Adhesive and peripheral systems and methods for medical devices

ABSTRACT

A repeater system may control a pump by using a repeater and a user interface. An adhesive patch system may be used for affixing a pump or other object to a human body. Such an adhesive patch system may include two sets of adhesive members, each member including an adhesive material on at least one side so as to attach to the body. The members of the first set are spaced to allow the members of the second set to attach to the body in spaces provided between the members of the first set, and the members of the second set are spaced to allow members of the first set to detach from the body without detaching the members of the second set. Also, fill stations and base stations are provided for personal pump systems.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.12/395,185, filed Feb. 27, 2009, and entitled Adhesive and PeripheralSystems and Methods for Medical Devices, now U.S. Pat. No. 9,339,603,issued on May 17, 2016, which is a continuation of U.S. patentapplication Ser. No. 11/704,897, filed on Feb. 9, 2007, and entitledAdhesive and Peripheral Systems and Methods for Medical Devices, nowU.S. Pat. No. 8,113,244, issued on Feb. 14, 2012, both of which arehereby incorporated herein by reference in their entireties. U.S. Pat.No. 8,113,244 claims priority to the following patent applications, eachof which is herein incorporated by reference in its entirety:

Ser. No. 60/772,313, filed Feb. 9, 2006 and entitled Portable InjectionSystem;

Ser. No. 60/789,243, filed Apr. 5, 2006 entitled Method of VolumeMeasurement for Flow Control; and

Ser. No. 60/793,188, filed Apr. 19, 2006 entitled Portable Injection andAdhesive System.

U.S. Pat. No. 9,339,603 is also a continuation of U.S. patentapplication Ser. No. 11/704,899, filed on Feb. 9, 2007, entitled FluidDelivery Systems and Methods, now U.S. Pat. No. 8,414,522, issued onApr. 9, 2013, both of which are hereby incorporated herein by referencein their entireties. U.S. Pat. No. 8,414,522 claims priority to thefollowing patent applications, each of which is herein incorporated byreference in its entirety:

Ser. No. 60/772,313, filed Feb. 9, 2006 and entitled Portable InjectionSystem;

Ser. No. 60/789,243, filed Apr. 5, 2006 entitled Method of VolumeMeasurement for Flow Control; and

Ser. No. 60/793,188, filed Apr. 19, 2006 entitled Portable Injection andAdhesive System.

U.S. Pat. No. 9,339,603 is also a continuation of U.S. patentapplication Ser. No. 11/704,886, filed on Feb. 9, 2007, entitledAdhesive and Peripheral Systems and Methods for Medical Devices, nowU.S. Pat. No. 8,545,445, issued on Oct. 1, 2013, both of which arehereby incorporated herein by reference in their entireties. U.S. Pat.No. 8,545,445 claims priority to the following patent applications, eachof which is herein incorporated by reference in its entirety:

Ser. No. 60/772,313, filed Feb. 9, 2006 and entitled Portable InjectionSystem;

Ser. No. 60/789,243, filed Apr. 5, 2006 entitled Method of VolumeMeasurement for Flow Control; and

Ser. No. 60/793,188, filed Apr. 19, 2006 entitled Portable Injection andAdhesive System.

U.S. Pat. No. 9,339,603 is also a continuation of U.S. patentapplication Ser. No. 11/704,896, filed on Feb. 9, 2007, entitled PumpingFluid Delivery Systems and Methods Using Force Application Assembly, nowU.S. Pat. No. 8,585,377, issued on Nov. 19, 2013, both of which arehereby incorporated herein by reference. U.S. Pat. No. 8,585,377 claimspriority to the following patent applications, each of which is hereinincorporated by reference in its entirety:

Ser. No. 60/772,313, filed Feb. 9, 2006 and entitled Portable InjectionSystem;

Ser. No. 60/789,243, filed Apr. 5, 2006 entitled Method of VolumeMeasurement for Flow Control; and

Ser. No. 60/793,188, filed Apr. 19, 2006 entitled Portable Injection andAdhesive System.

This application may also be related to Provisional Application No.60/889,007 entitled “Two-Stage Transcutaneous Inserter” which is herebyincorporated herein by reference in its entirety

FIELD OF THE INVENTION

This application relates generally to adhesive and peripheral systemsand methods for medical devices.

BACKGROUND

Many potentially valuable medicines or compounds, including biologicals,are not orally active due to poor absorption, hepatic metabolism orother pharmacokinetic factors. Additionally, some therapeutic compounds,although they can be orally absorbed, are sometimes required to beadministered so often it is difficult for a patient to maintain thedesired schedule. In these cases, parenteral delivery is often employedor could be employed.

Effective parenteral routes of drug delivery, as well as other fluidsand compounds, such as subcutaneous injection, intramuscular injection,and intravenous (IV) administration include puncture of the skin with aneedle or stylet. Insulin is an example of a therapeutic fluid that isself-injected by millions of diabetic patients. Users of parenterallydelivered drugs would benefit from a wearable device that wouldautomatically deliver needed drugs/compounds over a period of time.

To this end, there have been efforts to design portable devices for thecontrolled release of therapeutics. Such devices are known to have areservoir such as a cartridge, syringe, or bag, and to be electronicallycontrolled. These devices suffer from a number of drawbacks includingthe malfunction rate. Reducing the size, weight and cost of thesedevices is also an ongoing challenge.

SUMMARY OF THE INVENTION

In one embodiment of the invention, a repeater system is provided forcontrolling a medical device. Such a system may include a repeater and auser interface. The repeater may include circuitry (i) for, over a givenrange, receiving signals from at least one wearable medical device, (ii)for, over the given range, transmitting signals to the wearable medicaldevice, (iii) for, over a longer range exceeding the given range,transmitting the received signals to a user interface located remotelyfrom the patient, and (iv) for, over the longer range, receiving signalsfrom the user interface. The user interface may include circuitry (i)for receiving signals from the repeater, and (ii) for transmittingsignals to the repeater. The medical devices may be wearable orimplanted devices.

In some embodiments, the user interface's circuitry may also provide forthe reception of signals directly from the wearable device and thetransmission of signals directly to the wearable device. Also, therepeater's circuitry may be adapted to receive signals from multiplemedical devices.

In some embodiments, the repeater may include one or more of thefollowing: memory for logging received data, a processor for analyzingreceived data for the presence of a fault condition, and an alarm fornotifying a user of the presence of a fault condition. The faultcondition may include an occurrence of an event wherein the repeater isseparated from the wearable medical device by more than the given range.

In one embodiment of the invention, a repeater is adapted to control apatch-sized pump worn on a subject for delivering fluid to the subject.In this embodiment, the repeater may have circuitry (i) for, over agiven range, receiving signals from the pump, the received signalscontaining data relating to a volume of fluid delivered by the pump andrelating to an alarm condition, and (ii) for, over a longer rangeexceeding the given range, transmitting the received signals to aninterface for monitoring the volume of fluid delivered and the alarmcondition. Such a repeater's circuitry may also provide for, over thelonger range, receiving control signals from the interface, the controlsignals containing control information for controlling the pump, andfor, over the given range, transmitting the control signals to the pump.

Such a repeater may have the characteristics of the repeater describedabove in connection with the repeater system. In addition to or ininstead of having an alarm for an occurrence of an event wherein therepeater is separated from the wearable medical device by more than thegiven range, the repeater may also include an alarm for a flow occlusionor an air bubble detected in the pump.

In another embodiment of the invention, an adhesive patch system isprovided for affixation of an object to a human body. Such an adhesivepatch system may include two sets of adhesive members. In a first set ofthree or more members, each member includes an adhesive material on atleast one side so as to attach to the body upon application of pressure,the members disposed around a central region. Similarly, in the secondset of three or more members, each member includes an adhesive materialon at least one side so as to attach to the body upon application ofpressure, the members disposed around the central region. The members ofthe first set are spaced to allow the members of the second set toattach to the body in spaces provided between the members of the firstset, and the members of the second set are spaced to allow members ofthe first set to detach from the body without detaching the members ofthe second set.

In one embodiment of the adhesive patch system at least one member isperforated so as to allow facile tearing off of the member. Tearing offof the member may relieve irritation of the underlying skin. Also, thecentral region is adapted to secure a wearable medical device. Theadhesive patch may be semicircular. The adhesive patch may include apeelable backing strip. The members of the adhesive patch system may beattached to the central region by a fiber. The members of the first setmay be a first color while the members of the second set may be a secondcolor different from the first color.

Such an adhesive patch system may be used to attach an object to a humanbody by a method that includes the steps of: providing the first set ofthree or more members (each member of which, as noted above, includes anadhesive material on at least one side so as to attach to the body uponapplication of pressure, the members being disposed around a centralregion); attaching the first set of members to the body so that spacesare left between each of the members, so as to hold the object againstthe body; providing a second set of three or more members (each memberof which includes an adhesive material on at least one side so as toattach to the body upon application of pressure, the members beingdisposed around the central region); attaching the second set of membersto the body in the spaces between the members of the first set, so as tohold the object against the body with the second set of members; andafter attaching the second set of members to the body, removing thefirst set of members from the body.

The object being attached may be a pump for therapeutic of fluid to thebody through the skin. A cannula of such a pump may be passed throughthe skin to permit delivery of the fluid from the pump through the skin.In a preferred embodiment of the method, the cannula is not moved and isleft passing through the skin while the second set of members isattached to the body and while the first set of members is removed fromthe body.

Similarly, the object being attached may be a probe for measuring aparameter in the body through the skin. Such a probe may be passedthrough the skin. In a preferred embodiment of the method, the probe isnot moved and is left passing through the skin while the second set ofmembers is attached to the body and while the first set of members isremoved from the body.

The object being attached in such an adhesive patch system may beprovided with air passages to permit airflow to the body under theobject when the object is attached to the body.

An alternative adhesion system for affixing an object to a human bodyincludes a central member adapted to secure a wearable object and havingan adhesive material on at least one side so as to attach to the bodyupon application of pressure, and includes a plurality of peripheralmembers, each member including an adhesive material on at least one sideso as to attach to the body upon application of pressure, whereinfibrous connectors are provided for connecting each of the peripheralmembers to the central member. In a preferred embodiment, the fibrousconnectors are elastic.

In one embodiment of the invention, a method is provided for filling areservoir with a liquid therapeutic. Such a method may include providinga fill station having a substantially rigid fill-station base forholding the reservoir at a tilt, and a substantially rigid fill-stationcover attached to the fill-station base. The fill-station cover has afilling aperture for receiving fluid from a syringe. The fill-stationcover and the fill-station base define a volume so as to preventover-filling of the reservoir. Such a method also includes placing areservoir in the fill station, closing the fill-station cover over thereservoir, applying a syringe containing the liquid therapeutic to thefilling aperture, and ejecting the liquid therapeutic from the syringethrough the filling aperture into the reservoir. In a preferredembodiment, any air in the reservoir after the ejection step is removed.A window may be provided in the fill station cover to view the amount ofliquid in the reservoir. The amount of liquid may be estimated bycomparing the liquid level viewed through the window to a fluid-levelindicia.

In one embodiment of the invention, a base station is provided for apatch-sized infusion device, wherein the infusion device includes adisposable portion and a reusable portion, and the disposable portionand the reusable portion are connectable to each other via an attachmentmechanism associated with the reusable portion. The base stationincludes a receptacle for holding the reusable portion of the infusiondevice, the receptacle including a member for cooperating with thereusable portion's attachment mechanism. The base station may alsoinclude a recharger for recharging a battery in the reusable portion.The base station may also include a communication interface between aseparate computer and the reusable portion, in order to uploadinformation to or download information from the reusable portion.

These aspects of the invention are not meant to be exclusive and otherfeatures, aspects, and advantages of the present invention will bereadily apparent to those of ordinary skill in the art when read inconjunction with the appended claims and accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing features of the invention will be more readily understoodby reference to the following detailed description, taken with referenceto the accompanying drawings, in which:

FIG. 1 depicts a patient with a patch and a wireless handheld userinterface assembly;

FIG. 2A is a schematic diagram of a fluid-delivery device with feedbackcontrol;

FIG. 2B is a schematic diagram of a fluid-delivery device with feedbackcontrol and a reservoir;

FIG. 3 is a schematic diagram of a fluid-delivery device having anun-pressurized reservoir;

FIGS. 4A-4C are schematic sectional diagrams of various embodiments of aflow restrictor;

FIG. 5 shows a resilient dispensing assembly in series with a flowrestrictor;

FIG. 6 shows a dispensing assembly having a metering chamber and asensor;

FIG. 7 shows a dispensing assembly having a metering chamber with adispensing spring and a sensor;

FIG. 8 shows a sectional view of a dispensing assembly with an alternateacoustic path;

FIG. 9 shows a schematic view of a dispensing assembly;

FIG. 10 shows a diaphragm spring for use with a resilientvariable-volume dispensing chamber;

FIG. 11A shows a kinetic profile of an exemplary basal fluid delivery;

FIG. 11B shows a kinetic profile of an exemplary bolus fluid delivery;

FIG. 11C shows kinetic data representing a normal fluid delivery;

FIGS. 11D-11F show kinetic data representing various fault conditions;

FIG. 12 shows a flow chart of a sensing and reacting process of anembodiment of the fluid delivery device;

FIG. 13 shows a block diagram of a fluidic line with a pressuregeneration assembly;

FIG. 14 shows a block diagram of a fluidic line with a valving pump;

FIGS. 15A-15D show schematic diagrams of a pumping mechanism;

FIG. 16 shows a schematic diagram of a pumping mechanism;

FIG. 17 schematically shows a sectional view of an embodiment thatincludes a shape-memory-wire actuator capable of multiple pumping modes;

FIG. 18 schematically shows a sectional view of an embodiment thatincludes two shape-memory actuators and is capable of multiple pumpingmodes;

FIG. 19 schematically shows a sectional view of an embodiment thatincludes shape-memory actuators of differing lengths;

FIG. 20A-20B schematically show embodiments for attaching a shape memoryactuator;

FIGS. 21A-21B schematically show embodiments for attaching a shapememory actuator to a pumping mechanism;

FIGS. 22 and 23 show pumping mechanisms employing a finger;

FIG. 24 shows a pumping mechanism employing rotating projections;

FIG. 25 shows a pumping mechanism employing a plunger and barrel;

FIG. 26 shows a view of a shape-memory actuator in an expanded state;

FIG. 27 shows a view of a shape-memory actuator in a contracted state;

FIG. 28 shows a view of a pumping assembly employing a plunger andbarrel, and a shape-memory motor having a lever;

FIG. 29 shows a view of a pumping assembly employing a plunger andbarrel, and a shape-memory motor;

FIG. 30 shows a view of a pumping device employing a plunger and barreland a shape-memory motor having a wire in a shaft of the plunger;

FIG. 31 shows a flow line embodiment with a combined pump and reservoir;

FIG. 32 schematically shows a sectional view of a valving pump in aresting position;

FIG. 33 schematically shows a sectional view of the valving pump of FIG.32 in an intermediate position;

FIG. 34 schematically shows a sectional view of the valving pump of FIG.32 in an actuated position;

FIG. 35 schematically shows a sectional view of a pumping diaphragm foruse in a valving pump;

FIG. 36 shows a perspective view of a diaphragm spring for use in apumping diaphragm;

FIG. 37 schematically shows a sectional view of a valving pump employinga lever and a shape memory wire actuator;

FIG. 38 schematically shows a sectional view of an embodiment thatincludes a valving pump which employs a resilient cylindrical flexure;

FIG. 39 schematically shows a sectional view of an embodiment thatincludes a valving pump flexure having a resilient member and a rigidsupport;

FIG. 40 schematically shows a sectional view of a valving pump, in aresting state, with a diaphragm spring upstream of a flexible membrane;

FIG. 41 schematically shows a sectional view of the valving-pump of FIG.40, in an intermediate state;

FIG. 42 schematically shows a sectional view of the valving-pump of FIG.40, in an actuated state;

FIG. 43 schematically shows a sectional view of a valving-pump with adiaphragm spring upstream of a flexible membrane, in which a flexiblemembrane is circumferentially attached to a force application member;

FIG. 44 schematically shows a sectional view of a valving-pump with adiaphragm spring upstream of a flexible membrane, which includes a rigidball for transmitting force;

FIG. 45 schematically shows a sectional view of an embodiment thatincludes a valving pump having a resilient pump blade;

FIG. 46 schematically shows a sectional view of an embodiment thatincludes an alternative version of a resilient pump blade for use with avalving pump;

FIG. 47 schematically shows a sectional view of an embodiment thatincludes a valving pump having multiple force application members;

FIG. 48 schematically shows, in a resting or filling mode, a pumpingmechanism including a bell-crank driven valving-pump and a flow-biasingvalve;

FIG. 49 schematically shows the pumping mechanism of FIG. 48 in anactuated state.

FIG. 50 schematically shows a sectional view of a flow-biasing valve inaccordance with an embodiment of the invention having a raised valveseat and in a closed position;

FIG. 51 schematically shows a sectional view of the flow-biasing valveof FIG. 50 in an open position;

FIG. 52 schematically shows a sectional view of a flow-biasing valve inaccordance with an embodiment of the invention without a raised valveseat and in an open position;

FIG. 53 schematically shows a sectional view of the flow-biasing valveof FIG. 52, in a closed position;

FIG. 54 schematically shows forces that act upon a poppet in thevicinity of a valve outlet in accordance with embodiments of theinvention;

FIG. 55 schematically shows, in close-up view, forces that act upon apoppet in the vicinity of a valve inlet in accordance with embodimentsof the invention;

FIG. 56 schematically shows a flow-biasing valve with an adjustablecracking pressure in accordance with an embodiment of the invention;

FIGS. 57 and 58 show schematics for flow lines utilizing un-pressurizedreservoirs;

FIGS. 59A-59E shows schematics of a fluid flow in a fluid deliverydevice;

FIGS. 60A-60D shows exploded schematics of the fluid flow in a fluiddelivery device;

FIGS. 61A-61C show schematics of a fluid flow in a fluid deliverydevice;

FIGS. 62A and 62B show schematics of a stand alone device;

FIGS. 63A-63C show cross sectional schematics of embodiments of adevice;

FIGS. 64A-64D show cross section schematics of embodiments of a device;

FIGS. 65A-65B show cross section schematics of embodiments of aninfusion device connected to a fluid line;

FIGS. 66A-66D show cross section schematics of a sequence of inserting areservoir into a device;

FIGS. 67A-67F show schematics of embodiments of the fluid deliverydevice;

FIG. 68 is schematic of one embodiment of the portable pump embodimentof the device connected to a patient;

FIGS. 69A-69B show schematic views of the underside of the housing of adevice;

FIGS. 70-70D are a diagram depicting the various components available inembodiments of the fluid delivery device;

FIG. 71 schematically shows components which may be assembled to createa fluid delivery device in accordance with an embodiment of the device;

FIG. 72 shows a side view of a fluid-delivery device with an acousticvolume-measurement component;

FIG. 73 shows a printed circuit board for acoustic volume measurement;

FIG. 74 shows a pictorial view of an embodiment of a device;

FIG. 75 shows a pictorial sectional view of an embodiment of fluiddelivery device;

FIG. 76 shows an exploded pictorial view of an embodiment of a fluiddelivery device;

FIG. 77 shows an exploded view of components which may be assembled tocreate one embodiment of a fluid delivery device;

FIG. 78 shows an exploded view of an embodiment of the fluid deliverydevice;

FIG. 79 shows a top view of a base of one embodiment of the fluiddelivery device;

FIG. 80 shows the underside of the top of one embodiment of the fluiddelivery device;

FIGS. 81A-81C show a sequence to illustrate the process of sandwichingthe reservoir 20 between the top and base;

FIG. 82 shows an exploded top view of a device;

FIG. 83 shows an exploded view of the bottom of one embodiment of thedevice showing the fluid path assembly, the bottom housing and themembrane and adhesive;

FIG. 84 shows a bottom view of the base showing a bottom view of a fluidpath assembly;

FIGS. 85A-85D show exploded, partially exploded and non-exploded viewsof an embodiment of a device;

FIG. 86A shows a schematic of an infusion and sensor assembly having aninfusion device and analyte sensor connected;

FIG. 86B shows an exploded view of an infusion and sensor assembly asshown in FIG. 86A with introduction needles;

FIGS. 87A-87E shows a sequence of an embodiment of the infusion andsensor assembly being inserted into a device;

FIGS. 88A-88B show one embodiment of an inserter device in a sequencewith an infusion and sensor assembly;

FIGS. 88C-88D show a partial cut away view of the inserter in FIG.88A-88B;

FIG. 89A shows a front view of one embodiment of an inserter device forthe insertion of an infusion and sensor assembly;

FIG. 89B shows a rear view of insertion device of FIG. 89A;

FIG. 90 shows a perspective view of one embodiment of a cartridge for aninfusion and sensor assembly;

FIGS. 91A-91C show perspective front and side views of an inserterdevice for insertion of infusion and sensor assembly;

FIGS. 92A-92F schematically shows a temporal sequence for the operationof one embodiment of an inserter mechanism;

FIG. 92G shows an inserter mechanism having a catch and a cocking leverin a closed position;

FIG. 92H shows an inserter mechanism with a catch and a cocking lever inan open position;

FIGS. 93A-93C show a time-series for the insertion of a cannula into abase of a fluid delivery device;

FIGS. 94A-94C shows a temporal sequence for the insertion of a cannulainto a base with co-incident connection of the cannula to a fluid line;

FIG. 95 shows a top view of an adhesive patch for holding a fluiddelivery device;

FIG. 96 schematically shows a sectional view of a fluid-delivery deviceunder an adhesive patch;

FIG. 97 shows a perspective view of two overlapping adhesive patches forholding a fluid delivery device;

FIG. 98 shows a top view of two semicircular adhesive patch portions;

FIG. 99 shows a perspective view of two semicircular adhesive patchportions holding a fluid delivery device;

FIG. 100 shows a perspective view of a semicircular adhesive patchportion being removed by a patient;

FIG. 101 shows a perspective view of a fluid-delivery device being heldagainst a patient using multiple adhesive members and tethers;

FIG. 102A shows a clamp for assembling a device;

FIG. 102B shows a base of a fluid delivery device having keyholes forinserting clamps;

FIG. 102C shows a sectional view of a fluid delivery device assembledwith a clamp;

FIG. 103A shows a perspective view of a cam guide for use in assemblinga fluid delivery device;

FIG. 103B shows a top view of the cam guide of FIG. 103A;

FIG. 103C shows a perspective view of a clamp pin for use in assemblinga fluid delivery device;

FIG. 103D shows an embodiment of a fluid delivery device assembled usinga clamp pin and cam guide;

FIG. 104 shows a sectional view of a collapsible reservoir in accordancewith one embodiment;

FIG. 105 shows a perspective view the reservoir of FIG. 104;

FIG. 106A-106C shows a series of steps for securing a septum to a cap toproduce a reservoir in accordance with one embodiment;

FIG. 107 shows a reservoir filling station in accordance with oneembodiment;

FIGS. 108A-108B shows an embodiment of a reservoir filling station inboth the open (108A) an closed (108B) positions;

FIG. 109A shows a block diagram of one embodiment of a data acquisitionand control scheme for an embodiment of the fluid delivery system;

FIG. 109B shows a block diagram of one embodiment of a data acquisitionand control scheme for an embodiment of the fluid delivery system

FIG. 110A shows a flow chart describing the operation of a fluiddelivery device according to one embodiment;

FIG. 110B shows a flow chart describing the operation of a fluiddelivery device according to one embodiment;

FIG. 111 shows a block diagram of a user interface and fluid deliverycomponent in wireless communication with each other;

FIG. 112 shows a data flow diagram showing the use of an intermediatetransceiver in accordance with one embodiment;

FIG. 113 shows a block diagram for an intermediate transceiver inaccordance with one embodiment;

FIG. 114 shows a data flow diagram for a universal patient interface inaccordance with one embodiment;

FIG. 115 shows a non-disposable portion of the fluid delivery device anda battery recharger in an uncoupled state in accordance with oneembodiment;

FIG. 116 shows the non-disposable portion of the fluid delivery deviceand battery recharger of FIG. 115 in a docked state in accordance withone embodiment; and

FIG. 117 is a flowchart depicting a process for measuring the volume ofliquid delivered in a pump stroke, in accordance with an embodiment ofthe invention.

It should be noted that the foregoing figures and the elements depictedtherein are not necessarily drawn to a consistent scale or to any scale.

DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS Definitions

As used in this description and the accompanying claims, the followingterms shall have the meanings indicated, unless the context otherwiserequires:

A “user input” of a device includes any mechanism by which a user of thedevice or other operator can control a function of the device. Userinputs may include mechanical arrangements (e.g., switches,pushbuttons), wireless interfaces for communication with a remotecontroller (e.g., RF, infrared), acoustic interfaces (e.g., with speechrecognition), computer network interfaces (e.g., USB port), and othertypes of interfaces.

A “button” in the context of a user input such as the so-called “bolusbutton” discussed below may be any type of user input capable ofperforming a desired function, and is not limited to a pushbutton.

An “alarm” includes any mechanism by which an alert can be generated toa user or third party. Alarms may include audible alarms (e.g., aspeaker, a buzzer, a speech generator), visual alarms (e.g., an LED, anLCD screen), tactile alarms (e.g., a vibrating element), wirelesssignals (e.g., a wireless transmission to a remote controller orcaretaker), or other mechanism. Alarms may be generated using multiplemechanisms simultaneously, concurrently, or in a sequence, includingredundant mechanisms (e.g., two different audio alarms) or complementarymechanisms (e.g., an audio alarm, a tactile alarm, and a wirelessalarm).

“Fluid” shall mean a substance, a liquid for example, that is capable offlowing through a flow line.

“Impedance” shall mean the opposition of a device or flow line to theflow of fluid therethrough.

“Wetted” describes a component that comes into direct contact with thefluid during normal fluid delivery operations. Since a fluid is notlimited to a liquid, a “wetted” component will not necessarily becomewet.

A “patient” includes a person or animal who receives fluid from a fluiddelivery device, whether as part of a medical treatment or otherwise.

“Cannula” shall mean a disposable device capable of infusing fluid to apatient. A cannula as used herein can refer to a traditional cannula orto a needle.

“Analyte sensor” shall mean any sensor capable of determining thepresence of an analyte in a patient. The embodiments of analyte sensorsinclude, but are not limited to, sensors capable of determining thepresence of any viral, parasitic, bacterial or chemical analyte. Theterm analyte includes glucose. An analyte sensor may communicate withother components within the fluid delivery device (e.g., a controller ina non-disposable portion) and/or with a remote controller.

“Dispensing assembly sensor” shall mean a mechanism for determining thevolume of fluid present in the dispensing chamber.

A “sharp” shall mean anything that is capable of puncturing or poking ananimal's skin, especially a human's skin. A Sharp may include a cannula,a cannula insertion device, an analyte sensor, or an analyte sensorinsertion device. Sharps may be provided individually or may be providedtogether, for example, in a cartridge.

“Disposable” refers to a part, device, portion or other that is intendedto be used for a fixed duration of time, then discarded and replaced.

“Non-disposable” refers to a reusable portion that is intended to havean open-ended duration of use.

“Patch-sized” shall mean of a size sufficiently small as to be secured,by means such as adhesive or straps, to the skin of a patient and wornas a medical device over a course of administration of substancecontained within the device. A medical device small enough to functionas an implant is within the scope of this definition.

“Normally present finite fluid impedance” shall mean a finite fluidimpedance that is present in the routine course of fluid delivery, i.e.,when a fault condition (e.g., an occlusion) is absent.

A “passive” impedance is one that is not actively controlled during apumping cycle.

“Acoustic volume measurement” shall mean quantitative measurement of arelevant volume using acoustical techniques such as described in U.S.Pat. Nos. 5,349,852 and 5,641,892, as well as the techniques describedherein.

A “temperature sensor” includes any mechanism for measuring temperatureand communicating temperature information to a controller. The devicemay include one or more temperature sensors for measuring such things asskin temperature, AVS temperature, ambient temperature, and fluidtemperatures.

Embodiments of the device, pumping mechanism, system and methodsdescribed herein relate to fluid delivery including pumping and volumemeasurement of fluid as well as the actuation and control of same.Embodiments of the device include a portable or non-portable device forfluid delivery. Some embodiments of the device include a base portionthat is disposable and a top portion that is non-disposable. The deviceincludes embodiments where an infusion device is inserted through thebase portion and directly into a patient. These device embodiments arepatch pump devices. The patch pump may be adhered to the patient usingan adhesive, a strap, or other suitable arrangement. The adhesive mayhave a protective peelable strip which may be removed to expose theadhesive prior to use.

However, in other embodiments, the fluid delivery device is a portabledevice where tubing is connected to a fluid line. The tubing istypically connected to a patient through a cannula.

In some embodiments where a disposable base and non-disposable top areimplemented, the base portion includes parts that are wetted, while theparts included in the non-disposable top portion are typicallynon-wetted parts.

Various embodiments of the pumping mechanism include an upstream inletvalve, a pumping actuation member, a downstream exit valve and amoveable member. In some embodiments, the pumping actuation member anddownstream valve functions are implemented using the same device. Thepumping mechanism pumps fluid from a reservoir through a fluid line toan exit. The pumping mechanism is typically employed with anon-pressurized reservoir, however, the scope of the present inventionis not limited accordingly.

In one embodiment of the fluid delivery system, the device includes ananalyte sensor housing. An analyte sensor is introduced into the patientthrough the analyte sensor housing of the base portion of the device. Inthese embodiments, an infusion device is also introduced through acannula housing on the base portion of the device. In these embodiments,the device is worn by the user as a patch pump.

The system typically includes a controller, which may include a wirelesstransceiver. Thus, the device may be controlled exclusively or in partthrough a wireless controller device. The controller device may receiveinformation through wireless communication from the analyte sensorand/or the fluid delivery device. The patient or a third party cancontrol the function of the fluid delivery device using the controllerdevice.

In one embodiment of the fluid delivery device, the device is an insulinpump and the analyte sensor is a blood glucose sensor. The controller,receiving information relating both to the volume of insulin delivered(or the number of pump strokes over time) and blood glucose data,assists the user in programming the actuation schedule for the pumpmechanism.

An exemplary dispensing assembly and volume sensing device is describedherein. The dispensing assembly includes at least one microphone and aloudspeaker. The assembly determines the volume change in a dispensingchamber to determine the volume of fluid pumped. The volume sensing datais used to determine the status of the fluid delivery device. Thus,various controls may rely on the volume sensing data.

In an embodiment of the invention, a user configures the fluid-deliverydevice via a user interface in order to cause the fluid-delivery deviceto deliver a fluid in an appropriate manner. In one embodiment, the userinterface resides on a separate hand-held user-interface assembly thatmay communicate wirelessly with the patch. The patch may be disposable,or partially disposable.

An exemplary use of embodiments of the device is for the delivery ofinsulin to diabetic patients, but other uses include delivery of anyfluid, as described above. Fluids include analgesics to those in pain,chemotherapy to cancer patients and enzymes to patients with metabolicdisorders. Various therapeutic fluids may include small molecules,natural products, peptide, proteins, nucleic acids, carbohydrates,nanoparticulate suspensions, and associated pharmaceutically acceptablecarrier molecules. Therapeutically active molecules may be modified toimprove stability in the delivery device (e.g., by pegylation ofpeptides or proteins). Although illustrative embodiments herein describedrug-delivery applications, embodiments may be used for otherapplications including liquid dispensing of reagents for high throughputanalytical measurements such as lab-on-chip applications and capillarychromatography. For purposes of description below, terms “therapeutic”or “fluid” are used interchangeably, however, in other embodiments, anyfluid, as described above, can be used. Thus, the device and descriptionincluded herein are not limited to use with therapeutics.

Typical embodiments include a reservoir for holding a supply of fluid.In the case of insulin, the reservoir may be conveniently sized to holdan insulin supply sufficient for delivery over one or more days. Forexample, a reservoir may hold about 1 to 2 ml of insulin. A 2 ml insulinreservoir may correspond to about 3 days supply for about 90% ofpotential users. In other embodiments, the reservoir can be any size orshape and can be adapted to hold any amount of insulin or other fluid.In some embodiments, the size and shape of the reservoir is related tothe type of fluid the reservoir is adapted to hold. The fluid reservoirmay be eccentrically or irregularly shaped and/or may be keyed in orderto deter incorrect installation or usage.

Some embodiments of the fluid delivery device are adapted for use bydiabetics, thus, in these embodiments, the device delivers insulin whichsupplements or replaces the action of the patient's pancreatic isletbeta cells. Embodiments adapted for insulin delivery seek to mimic theaction of the pancreas by providing both a basal level of fluid deliveryas well as bolus levels of delivery. Basal levels, bolus levels andtiming can be set by the patient or another party by using a wirelesshandheld user interface. Additionally, basal and/or bolus levels can betriggered or adjusted in response to the output of an integral orexternal analyte sensor, such as a glucose monitoring device or bloodglucose sensor. In some embodiments, a bolus can be triggered by apatient or third party using a designated button or other input meanslocated on the fluid-delivery device. In still other embodiments, thebolus or basal can be programmed or administered through a userinterface located on the fluid delivery device.

FIG. 1 shows a patient 12 wearing a fluid-delivery device 10 and holdinga wireless user interface assembly 14 for monitoring and adjustingoperation of the fluid-delivery device 10, in accordance with anexemplary embodiment of the present invention. The user interfaceassembly 14 typically includes apparatus for entering information (suchas touch-screen or keypad) and for transmitting information to the user(such as an LCD display, a speaker or a vibrating alarm). The fluiddelivery device is typically small and lightweight enough to remaincomfortably adhered to the patient for several days.

The fluid delivery device 10 is shown worn on the arm of a patient 12 inFIG. 1. In other embodiments, the fluid-delivery device 10 may be wornat other positions on the patient where the particular fluid beingdelivered can be utilized advantageously by the patient's body. Forexample, fluid may be delivered advantageously to the patient'sabdominal area, kidney area, leg or otherwise.

Referring now to FIG. 2A, a schematic representation of a fluid deliverydevice 10 having a feedback loop 360 from a dispensing assembly 120 to apumping assembly 16 is shown. The pumping assembly 16 pumps fluid to thedispensing assembly 120; the fluid then exits through an exit assembly17, which includes a flow restrictor 340 and an output. The outputtypically includes a cannula and leads to a patient. The dispensingassembly 120 may include a resilient, variable-volume dispensing chamberand at least one microphone and a loudspeaker for measuring parametersrelated to flow through the output over time. The feedback loop 360allows adjustment of the operation of the pumping assembly 16 based onrepeated measurements made by the sensor. The flow restrictor 340creates high impedance between the dispensing assembly 120 and theoutput of the flow line 5010. The flow restrictor 340 could be, forexample, a section of narrow-bore tubing or microtubing. Referring nowto FIG. 2B, in one embodiment, the pumping assembly 16 pumps fluid froma reservoir 20 to a dispensing assembly 120.

Referring now to FIG. 3, a block diagram of a further embodimentemploying fluidic principles is shown. A flow line 310 couples areservoir 20, a pumping assembly 16, a dispensing assembly 120, and anexit assembly 17. The exit assembly 17 may include a high impedance flowrestrictor 340 and an infusion device 5010—for example, a cannula. Theoutput of the flow restrictor 340 is sent to the infusion device 5010for delivery to a patient. The flow restrictor 340 has a higher flowimpedance than that of the portion of the flow line 310 upstream of thedispensing assembly 120. Therefore, the pumping assembly 16 is capableof pumping fluid into the dispensing assembly 120 faster than the fluidcan exit the exit assembly 17. The dispensing assembly 120 may include avariable volume dispensing chamber 122 having a resilient wall. Inembodiments presented below, the resilient wall is a membrane. Examplesof membrane materials include silicone, NITRILE, and any other materialhaving desired resilience and properties for functioning as describedherein. Additionally, other structures could serve the same purpose.Upon receiving a charge of fluid as a result of the action of thepumping assembly 16, the resilience of the membrane will allow thechamber 122 to first expand and then to provide the delivery pressurerequired to drive the fluid contents of the dispensing assembly 120 pastthe flow restrictor 340 to a patient. When equipped with an appropriatesensor (examples of which are described below), the dispensing assembly120 may measure fluid flow through the variable volume dispensingchamber 122 and may provide feedback through the feedback loop 360 tocontrol the timing and/or rate at which the pumping assembly 16 pumps orpartially fills the dispensing chamber 122, thereby delivering a desireddose at a desired rate to a patient.

Referring again to FIG. 3, additionally, the flow restrictor 340prevents fluid flow above a specified flow rate. Furthermore, sincepressurized fluid delivery is accomplished through the interaction ofthe pumping assembly 16, the dispensing assembly 120, and the flowrestrictor 340, a non pressurized reservoir 20 can be employed.

Still referring to FIG. 3, the feedback loop 360 may include acontroller 501. The controller 501 may include a processor and controlcircuitry for actuating a pumping assembly 16 to pump fluid to thedispensing assembly 120. The controller 501 repeatedly receives aparameter related to fluid flow from a sensor, which may be integral tothe dispensing assembly 120, and uses this parameter to control thepumping assembly 16 to achieve a desired flow through the output. Forexample, the controller 501 can adjust the timing or extent of actuationof the pumping assembly 16 to achieve a desired basal or bolus flow rateand/or to deliver a desired basal or bolus cumulative dose. Indetermining the timing or extent of pumping, the controller 501 may usethe output of the sensor (not shown) to estimate (amongst other things)the rate of fluid flow, cumulative fluid flow, or both, and then, basedon the estimation, determine an appropriate compensatory action. In thevarious embodiments, pumping may occur in pulses which can deliveranywhere between 10⁻⁹ liters per pulse to microliters per pulse. A basalor bolus dose may be achieved by delivering multiple pulses. (Examplesof basal and bolus dosing are shown and described below).

The use of a partially collapsible non pressurized reservoir 20 mayadvantageously prevent the buildup of air in the reservoir as the fluidin the reservoir is depleted. The reservoir 20 may be connected to thefluid line 310 through a septum (not shown). Air buildup in a ventedreservoir could prevent fluid egress from the reservoir 20, especiallyif the system is tilted so that an air pocket intervenes between thefluid contained in the reservoir and the septum of the reservoir 20.Tilting of the system is expected during normal operation as a wearabledevice. FIGS. 104-106C depict various embodiments and views of oneembodiment of the reservoir. Additionally, further description of thereservoir is included below.

Referring now to FIGS. 4A-4C, various embodiments of the flow restrictor340 are shown. Referring now to FIG. 4A, the flow restrictor is a moldedflow channel 340, which may be a molded groove in a base (not shown). Inone embodiment, the cross section of the molded flow channel 340 isapproximately 0.009 inches. In this embodiment, the flow restrictor 340is molded into an apparatus. Referring now to FIG. 4B, microtubing 340is shown as an alternate embodiment flow restrictor. In one embodiment,the microtubing has an internal diameter of approximately 0.009 inches.Both the molded flow channel and the microtubing use a long path havinga small internal diameter or cross section to impart flow impendence.Referring now to FIG. 4C, a precision orifice is shown as a flowrestrictor 340. In one embodiment, the precision orifice is a plate witha laser drilled hole. In alternate embodiments, any flow impendencedevice or method known in the art can be used.

In contrast to prior-art fluid delivery systems that have an activedownstream valve, which may be generally considered to create, in afunctional sense, an infinite fluid impedance, the flow restrictor 340creates a finite fluid impedance. The impedance is also normallypresent; in contrast to prior-art systems than may occasionally beimpeded due to an occlusion. As a result of the finite nature of thefluid impedance, in embodiments that include a dispensing chamber 122,fluid may leak through the exit even while the dispensing chamber 122 isexpanding.

FIGS. 5-8 schematically show sectional views of illustrative embodimentsof the dispensing assembly 120. It is to be understood that the deliveryof fluid for other purposes, such as industrial processes, is within thescope of the present invention, and that the description in particularterms is by way of example only. As shown in FIG. 5, the dispensingassembly 120 may include the variable volume dispensing chamber 122 anda sensor 550. The variable volume dispensing chamber 122 includes aresilient dispensing diaphragm 125, which allows the chamber 122 toexpand and contract depending on the flow of fluid into and out of thedispensing assembly 120. In certain embodiments of the invention, thevariable-volume dispensing chamber 122 may be detachable from otherelements of the dispensing assembly 120, as further discussed herein.The concept of the resilient dispensing diaphragm 125 allowing thechamber 122 to expand and contract is illustrated by the double headedarrow. Metering chamber 122 is considered to comprise a portion of aline 110 characterized by a fluid flow, which is designated, in FIG. 5,by arrow 112. Neither the position nor the nature of the termination offluid flow 112 or line 110 need limit the scope of the present inventionas claimed in certain of the claims appended hereto. The flow restrictor340 causes fluid to leave the dispensing chamber 122 more slowly thanfluid enters the chamber 122 when pumped into the chamber 122 by thepumping assembly 16. As a consequence, the dispensing chamber 122expands and is pressurized as a fluid charge enters. Dispensingdiaphragm 125, deformed by virtue of the expansion of dispensing chamber122, provides the force needed to deliver the metered volume past theflow restrictor 340 to the exit assembly 17. As discussed above, thesensor 550 repeatedly measures a parameter, such as a displacement, or athermodynamic variable or capacitance, that can be related to the volumeof the resilient dispensing chamber 122. The volume measurementsproduced by the sensor 550 may be used to control, through a feedbackloop, the timing and rate at which the pumping assembly pumps fluid tothe dispensing chamber 122 so that the proper flow of fluid is deliveredto exit assembly 17 and to a subsequent line, and thence, for example,to the patient. The sensor 550 may employ, for example, acoustic volumesensing (described in more detail below), or other methods (optical, orcapacitive, for other examples) for determining a volume, or avolume-related parameter. Acoustic volume measurement technology is thesubject of U.S. Pat. Nos. 5,575,310 and 5,755,683 assigned to DEKAProducts Limited Partnership, as well as the provisional U.S. patentapplication entitled “METHOD OF VOLUME MEASUREMENT FOR FLOW CONTROL”,Ser. No. 60/789,243, filed Apr. 5, 2006, all of which are herebyincorporated herein by reference. Fluid volume sensing in the nanoliterrange is possible with this embodiment, thus contributing to highlyaccurate and precise monitoring and delivery. Other alternate techniquesfor measuring fluid flow may also be used; for example, Doppler-basedmethods; the use of Hall-effect sensors in combination with a vane orflapper valve; the use of a strain beam (for example, related to aflexible member over a fluid chamber to sense deflection of the flexiblemember); the use of capacitive sensing with plates; or thermal time offlight methods.

Referring now to FIGS. 6 through 9, embodiments are shown in which asensor utilizes acoustic volume sensing (AVS) technology. A firstdiscussion refers to embodiments depicted in FIGS. 6 and 7. Thedispensing assembly 120 has a sensor that includes a reference chamber127, and a variable volume measurement chamber 121 that is coupled by aport 128 to a fixed-volume chamber 129. While the invention may bepracticed with a reference chamber 127, as shown in FIGS. 6 and 7, incertain other embodiments of the invention, no reference volume isprovided. It is to be understood that volume 129 is referred to, herein,as “fixed” as a matter of terminology, but that the actual volume mayvary slightly, on the time scale of acoustic excitation, as when theregion referred to as fixed volume 129 is driven by a speaker diaphragm.Fluid flows from the pumping assembly 16 to an input 123, through theresilient dispensing chamber 122, and out of an exit channel 124. Due tothe high downstream impedance, as fluid enters the dispensing chamber122, the dispensing diaphragm 125 expands into the variable volumechamber 121. An electronics assembly, which may be arranged on a printedcircuit board 126, has a loudspeaker 1202, a sensing microphone 1203,and a reference microphone 1201 for measuring acoustic parametersassociated with a gas (typically air) in the variable volume chamber121, the volume of which is defined by the position of the dispendingdiaphragm 125. Sound waves induced by the loudspeaker 134 travel throughthe fixed volume chamber 129 to the variable volume chamber 121 via theport 128; sound waves also travel to the reference chamber 127. As thedispensing diaphragm 125 moves with the flow of fluid through the flowline, the volume of air in the variable volume chamber 121 varies,causing related changes in its acoustic characteristics, which may bedetected by the loudspeaker and microphone 1203. For the same acousticstimulations, the reference microphone 1201 may detect acousticcharacteristics of the fixed reference volume 127. These referencemeasurements may, for example, be used to factor out imprecision and toreject common-mode inaccuracies in acoustic stimulation, and othererrors. The volume of fluid displaced may be determined by comparing themeasured volume of the variable volume chamber 121 to an initial volumeof the variable volume chamber 121. Since the total combined volume ofthe dispensing chamber 122 and variable volume chamber 121 staysconstant, the absolute volume of the dispensing chamber 122 can also beestimated.

The embodiment shown in FIG. 6 utilizes an inherently resilientdispensing diaphragm 125, while the embodiment shown in FIG. 7 utilizesa resilient dispensing spring 130, which when combined with a dispensingdiaphragm 125, increases the resiliency of the dispensing chamber 122and may allow the use of a more compliant (i.e., less resilient)dispensing diaphragm 125 than would be required in the embodiment shownin FIG. 5. The dispensing spring 130 is typically positioned adjacent tothe dispensing diaphragm 125 on a side of the diaphragm 125 opposite tothe dispensing chamber 122.

Alternately, to reduce background noise from the microphone, theloudspeaker 1202 and the sensing microphone 1203 may be coupled to thevariable volume chamber 121 via separate ports. As schematically shownin FIG. 8, a loudspeaker 1202 generates pressure waves in a fixedloudspeaker volume 6000 which is acoustically coupled with the variablevolume chamber 121 via a loudspeaker port 6020. Pressure waves travelfrom the loudspeaker 1202, through the loudspeaker port 6020 to thevariable volume chamber 121 and then through a microphone port 6010before being recorded by the sensing microphone 1203. The loudspeakerport 6020 may include a tube portion 6040 with a flared aperture 6030.The flared aperture 6030 serves to create a uniform length along whichsound waves travel for all axial paths of the tube portion 6040. Forexample, the tube portion 6040 can have the geometry of a cylinder, suchas a right cylinder or right circular cylinder. A similarly flaredaperture may also adjoin a tube portion to define the microphone port6010. In contrast to the AVS sensor of FIGS. 6 and 7, in the embodimentof FIG. 8, pressure waves traveling from the loudspeaker 1202 do nothave a direct path to the sensing microphone 1203. Thus, pressure wavesfrom the loudspeaker 1202 are prevented from directly impacting thesensing microphone 1203 without first passing through the variablevolume 121. A lower background signal is therefore received by themicrophone and a better signal/noise ratio is achieved. Additionally, anupper shelf 6050 may be included in any of the embodiments of FIGS. 6-8advantageously reducing the volume of the reference chamber 127.

In embodiments to be further described, it may be convenient to separatethe sensor and metering chamber portions of the dispensing assembly suchthat the dispensing chamber is detachable and disposable. In this case,the dispensing chamber resides in a disposable section of the patch,while the sensor resides in the reusable section. The dispensing chambermay be bounded by a resilient fluid dispensing diaphragm (as shown inFIG. 6 as 122 and 124). Alternately, as in FIG. 7, the dispensingchamber 122 may be bounded by a compliant diaphragm 125. In this case, adispensing spring 130 can be used to impart resiliency on the dispensingchamber 122. When the sensor 550 and dispensing chamber 122 are broughttogether, the dispensing spring 130 covers the compliant dispensingdiaphragm 125. The dispensing spring 130 and dispensing diaphragm 125may alternately be employed as a single part defining the dispensingchamber 122.

As shown in FIG. 9, an alternate embodiment of the dispensing assemblyis shown. In an embodiment of dispensing assembly 120 depicted in FIG.9, variable-volume measurement chamber 121 shares a compliant wall (hereshown as compliant diaphragm 125) with dispensing chamber 122. Port 128acoustically couples measurement chamber 121 to fixed volume chamber129, so as to form an acoustically contiguous region designatedgenerally by numeral 1290. A compressible fluid (typically, air, oranother gas) fills the acoustically contiguous region 1290 and isexcited by a driving member 1214, itself driven by an actuator 1216.Driving member 1214 may be a diaphragm of a speaker, such as a hearingaid speaker, where actuator 1216 is a voice coil solenoid orpiezoelectric element, for example. Within the scope of the invention,driving member 1214 may also be coextensive with actuator 1216, such aswhere driving member 1214 may, itself, be a piezoelectric element.Driving member 1214 may be contained within a driver module 1212 thatmay contain, on a side of driving member 1214 distal to fixed volume129, a reference volume 1220. However, reference volume 1220 istypically not employed in practice of the invention.

A reference microphone 1208 is shown in acoustic communication withfixed volume 129, while a signal microphone 1209 is acoustically coupledto measurement chamber 121. The volume of measurement region 121 may bedetermined from electronic signals provided by one or more microphones1208, 1209 on the basis of pressure variations (or, equivalently,acoustic signal) measured at their respective positions within theacoustically contiguous region 1290. Phase measurements may be performedby comparing the phase of response at one or more microphones relativeto the phase of acoustic excitation or relative to the phase of responseat a position of another microphone. The volume of measurement region121, and, by implication, of dispensing chamber 122, is determined, onthe basis of phase and/or amplitude measurements, as discussed below, bya processor 1210, which derives power from power source 1211, shown,representatively, as a battery.

For the purposes of precise delivery of minute amounts of therapeuticagents, the delivery of small, but very accurately metered, quantitiesper pump stroke is desirable. However, if minute volumes of fluid are tobe pumped through line 110 during the course of each pump stroke,extremely high resolution is required of the metering process.Consequently, in accordance with embodiments of the present invention,changes in volume are measured by sensor 550 with a resolution of atleast 10 nanoliters. Measurements of resolution 0.01% of the emptyvolume of measurement region 121 may be achieved in some embodiments ofthe invention. In accordance with other embodiments of the invention,sensor 550 provides resolution of better than 13 nanoliters. In otherembodiments yet, sensor 550 provides resolution of better than 15nanoliters, and in yet further embodiments, resolution of better than 20nanoliters is provided. In such cases, the total volume of acousticallycontiguous region 1290 may be less than 130 μl, and, in otherembodiments, less than 10 μl.

In accordance with various embodiments of the present invention, use maybe made of a priori modeling of the response of the volume of dispensingchamber 122, and, consequently of variable-volume chamber 121 (which mayalso be referred to, herein, as a “metering volume”), based upon thefilling of the dispensing chamber due to a pumped volume of fluidentering through input 123. While other models are within the scope ofthe present invention, one model that may be employed expresses thevolume of fluid within dispensing chamber 122, in response to a pumpedinflux of fluid and a outlet of fixed flow impedance, as the sum of abaseline volume V_(B) and an exponentially decaying volume characterizedby a peak displacement V_(D), such that the metering chamber volumeduring a measurement is characterized as a function of time t, as:

$V = {{V_{D}\mspace{14mu}{\exp\left( \frac{- t}{\tau} \right)}} + {V_{B}.}}$

In order to fit a parameterization of the modeled exponential decay (orother functional model) to a succession of acoustic measurements, theresponse of systems such as depicted in FIGS. 6 through 9 is developedas follows. For purposes of modeling the response, port 128 ischaracterized by a length l and a diameter d. The pressure and volume ofan ideal adiabatic gas can be related by PV^(γ)=K, where K is a constantdefined by the initial conditions of the system. The ideal adiabatic gaslaw can be written in terms of a mean pressure, P, and volume, V, and asmall time-dependent perturbation on top of those pressures, p(t), v(t):(P+p(t))(V+v(t))^(γ) =K.

Differentiating this equation yields{dot over (p)}(t)(V+v(t))^(γ)+γ(V+v(t))^(γ−1)(P+p(t)){dot over (v)}(t)=0Or, simplifying,

${{\overset{.}{p}(t)} + {\gamma\frac{P + {p(t)}}{V + {v(t)}}{\overset{.}{v}(t)}}} = 0$

If the acoustic pressure levels are much less than the ambient pressurethe equation can be further simplified to:

${{\overset{.}{p}(t)} + {\frac{\gamma\; P}{V}{\overset{.}{v}(t)}}} = 0.$

Applying the ideal gas law, P=ρ RT, and substituting in for pressuregives the result:

${{\overset{.}{p}(t)} + {\frac{\gamma\;{RT}\mspace{14mu}\rho}{V}{\overset{.}{v}(t)}}} = 0.$

This can be written in terms of the speed of sound, a=√{square root over(γRT)}, as:

${{\overset{.}{p}(t)} + {\frac{\rho\; a^{2}}{V}{\overset{.}{v}(t)}}} = 0.$

Also, an acoustic impedance for a volume is defined as:

$Z_{v} = {\frac{p(t)}{\overset{.}{v}(t)} = {{- \frac{1}{\left( \frac{V}{\rho\; a^{2}} \right)s}} = {{- \frac{\rho\; a^{2}}{V}} \cdot {\frac{1}{s}.}}}}$

In accordance with one set of models, the acoustic port is modeledassuming that all of the fluid in the port essentially moves as a rigidcylinder reciprocating in the axial direction. All of the fluid in thechannel (port 128) is assumed to travel at the same velocity, thechannel is assumed to be of constant cross section, and the “endeffects” resulting from the fluid entering and leaving the channel areneglected.

Assuming laminar flow friction of the form Δp=Rρ{dot over (v)}, thefriction force acting on the mass of fluid in the channel can bewritten: F=RρA²{dot over (x)}.

A second order differential equation can then be written for thedynamics of the fluid in the channel:ρLA{umlaut over (x)}=ΔpA−RρA ² {dot over (x)}

or, in terms of volume flow rate:

$\overset{¨}{v} = {{{- \frac{RA}{L}}\overset{.}{v}} + {\Delta\; p{\frac{A}{\rho\; L}.}}}$

The acoustic impedance of the channel can then be written:

$Z_{p} = {\frac{\Delta\; p}{\overset{.}{v}} = {\frac{\rho\; L}{A}{\left( {s + \frac{RA}{L}} \right).}}}$

Using the volume and port dynamics define above, the acoustic volumesensor system can be described by the following system of equations(with index k denoting the speaker, and r denoting the resonator):

${{\overset{.}{p}}_{0} - {\frac{\rho\; a^{2}}{V_{0}}{\overset{.}{v}}_{k}}} = 0.$

Following the same convention,

$\left. {{\overset{.}{v}}_{k} > 0}\Rightarrow{{\overset{.}{p}}_{1} < {0\mspace{14mu}{and}\mspace{14mu}{\overset{.}{v}}_{r}} > 0}\Rightarrow{{\overset{.}{p}}_{1} > 0} \right.,{{{\overset{.}{p}}_{1} + {\frac{\rho\; a^{2}}{V_{1}}\left( {{\overset{.}{v}}_{k} - {\overset{.}{v}}_{r}} \right)}} = 0.}$

In addition,

$\left. {{\overset{.}{v}}_{r} > 0}\Rightarrow{{\overset{.}{p}}_{2} < 0} \right.,{{{\overset{.}{p}}_{2} + {\frac{\rho\; a^{2}}{V_{2\;}}{\overset{.}{v}}_{r}}} = 0.}$

The volume tends to accelerate in a positive direction if p₂ is largerthan p₁.

${\overset{¨}{v}}_{r} = {{{- \frac{RA}{L}}{\overset{.}{v}}_{r}} + {\frac{A}{\rho\; L}{\left( {p_{2} - p_{1}} \right).}}}$

Reducing the number of equations (treating p₀ as input), andsubstituting

${{\overset{.}{v}}_{k} = {\frac{V_{0}}{\rho\; a^{2}}{\overset{.}{p}}_{0}}},{{{\overset{.}{p}}_{1} + {\frac{V_{0}}{V_{1\;}}{\overset{.}{p}}_{0}} - {\frac{\rho\; a^{2}}{V_{1}}{\overset{.}{v}}_{r}}} = 0}$${{\overset{.}{p}}_{2} + {\frac{\rho\; a^{2}}{V_{2}}{\overset{.}{v}}_{r}}} = 0$${\overset{¨}{v}}_{r} = {{{- \frac{RA}{L}}{\overset{.}{v}}_{r}} + {\frac{A}{\rho\; L}p_{1}} - {\frac{A}{\rho\; L}{p_{2}.}}}$

This leads to one simple expression using these equations:

${\frac{\rho\; a^{2}}{V_{2}}{\overset{.}{v}}_{r}} = {{\frac{V_{1}}{V_{2}} \cdot \left( {\frac{\rho\; a^{2}}{V_{1}}{\overset{.}{v}}_{r}} \right)} = {{\frac{V_{1}}{V_{2}}{\overset{.}{p}}_{1}} + {\frac{V_{0}}{V_{2}}{\overset{.}{p}}_{0}}}}$${{\overset{.}{p}}_{2} + {\frac{V_{0}}{V_{2}}{\overset{.}{p}}_{0}} + {\frac{V_{1}}{V_{2}}{\overset{.}{p}}_{1}}} = 0$${{{V_{0}{\overset{.}{p}}_{0}} + {V_{1}{\overset{.}{p}}_{1}}} = {{{{- V_{2}}{\overset{.}{p}}_{2}} - \frac{{V_{0}{\overset{.}{p}}_{0}} + {V_{1}{\overset{.}{p}}_{1}}}{{\overset{.}{p}}_{2}}} = V_{2}}},{or}$${{V_{0}p_{0}} + {V_{1}p_{1}}} = {{{{- V_{2}}p_{2}} - \frac{{V_{0}p_{0}} + {V_{1}p_{1}}}{p_{2}}} = V_{2}}$

These equations can also be expressed in transfer function form. The“cross-speaker” transfer function, p₁/p₀, is:

${{s \cdot p_{1}} + {\frac{V_{0}}{V_{1}}{s \cdot p_{0}}} - {\frac{\rho\; a^{2}}{V_{1}}{s \cdot v_{r}}}} = 0$${{s \cdot p_{2}} + {\frac{\rho\; a^{2}}{V_{2}}{s \cdot v_{r}}}} = 0$${s^{2} \cdot v_{r}} = {{{- \frac{RA}{L}}{s \cdot v_{r}}} - {\frac{A}{\rho\; L}p_{1}} + {\frac{A}{\rho\; L}p_{2}}}$$p_{2} = {{- \frac{\rho\; a^{2}}{V_{2}}}v_{r}}$${s^{2}v_{r}} = {{{{- \frac{RA}{L}}{s \cdot v_{r}}} + {\frac{A}{\rho\; L}\left( {- \frac{\rho\; a^{2}}{V_{2}}} \right)V_{r}} - {\frac{A}{\rho\; L}{p_{1}\left( {s^{2} + {\frac{RA}{L}s} + \frac{{Aa}^{2}}{{LV}_{2}}} \right)}v_{r}}} = {{- \frac{A}{\rho\; L}}p_{1}}}$$v_{r} = {\frac{{{- A}/\rho}\; L}{s^{2} + {\frac{RA}{L}s} + \frac{{Aa}^{2}}{{LV}_{2}}}p_{1}}$or$\frac{p_{1}}{p_{0}} = {{- \frac{V_{0}}{V_{1}}}\frac{s^{2} + {2{\zeta\omega}_{n}s} + {\alpha\;\omega_{n}^{2}}}{s^{2} + {2{\zeta\omega}_{n}s} + \omega_{n}^{2}}}$where${\omega_{n}^{2} = {\frac{a^{2}A}{L}\left( {\frac{1}{V_{1}} + \frac{1}{V_{2}}} \right)}};{\zeta = \frac{RA}{2L\;\omega_{n}}};{{{and}\mspace{14mu}\alpha} = {\frac{V_{1}}{V_{1} + V_{2}}.}}$

Similarly, the “cross system” transfer function, based on measurementson either end of port 128, is p₂/p₀, is given by:

${{s \cdot p_{1}} + {\frac{V_{0}}{V_{1}}{s \cdot p_{0}}} - {\frac{\rho\; a^{2}}{V_{1}}{s \cdot v_{r}}}} = 0$${{s \cdot p_{2}} + {\frac{\rho\; a^{2}}{V_{2}}{s \cdot v_{r}}}} = 0$${s^{2} \cdot v_{r}} = {{{- \frac{RA}{L}}{s \cdot v_{r}}} - {\frac{A}{\rho\; L}p_{1}} + {\frac{A}{\rho\; L}p_{2}}}$$p_{1} = {{\frac{\rho\; a^{2}}{V_{1}}v_{r}} - {\frac{V_{0}}{V_{1}}p_{0}}}$${s^{2}v_{r}} = {{{- \frac{RA}{L}}{s \cdot v_{r}}} - {{\frac{A}{\rho\; L} \cdot \frac{\rho\; a^{2}}{V_{1}}}v_{r}} - {\frac{A}{\rho\; L}\left( {{- \frac{V_{0}}{V_{1}}}p_{0}} \right)} + {\frac{A}{\rho\; L}p_{2}}}$$v_{r} = {{\frac{\frac{{AV}_{0}}{\rho\;{LV}_{1}}}{s^{2} + {\frac{RA}{L}s} + \frac{{Aa}^{2}}{{LV}_{1}}}p_{0}} + {\frac{\frac{A}{\rho\; L}}{s^{2} + {\frac{RA}{L}s} + \frac{{Aa}^{2}}{{LV}_{1\;}}}p_{2}}}$${{s \cdot p_{2}} + {\frac{\rho\; a^{2}}{V_{2}}{s \cdot \left\lbrack {{\frac{\frac{{AV}_{0}}{\rho\;{LV}_{1}}}{s^{2} + {\frac{RA}{L}s} + \frac{{Aa}^{2}}{{LV}_{1}}}p_{0}} + {\frac{\frac{A}{\rho\; L}}{s^{2} + {\frac{RA}{L}s} + \frac{{Aa}^{2}}{{LV}_{1}}}p_{2}}} \right\rbrack}}} = {{{0\left\lbrack {s^{2} + {\frac{RA}{L}s} + \frac{{Aa}^{2}}{{LV}_{1}} + \frac{{Aa}^{2}}{{LV}_{2}}} \right\rbrack}p_{2}} = {{{- \frac{{Aa}^{2}}{{LV}_{2}}} \cdot \frac{V_{0}}{V_{1}}}p_{0}}}$$\frac{p_{2}}{p_{0}} = {{- \frac{V_{0}}{V_{1}}}\frac{\frac{{Aa}^{2}}{{LV}_{2}}}{s^{2} + {\frac{RA}{L}s} + {\frac{{Aa}^{2}}{{LV}_{2}}\; \cdot \frac{V_{1} + V_{2}}{V_{1}}}}}$$\frac{p_{2}}{p_{0}} = {{- \frac{V_{0}}{V_{1}}}\frac{\alpha\;\omega_{n}^{2}}{s^{2} + {2{\zeta\omega}_{n}s} + \omega_{n}^{2}}}$Volume Estimation Using Cross-System Phase

Similarly, using the same principles, a transfer function is readilyderived, expressing a pressure in the fixed volume chamber 129 in termsof the pressure in the variable volume chamber 121 to which it iscoupled via port 128. In particular, the transfer function is:

$\begin{matrix}{\frac{p_{2}}{p_{1}} = \frac{1}{{\frac{V_{2}L_{p}}{a^{2}A_{p}}s^{2}} + {\frac{{RV}_{2}}{a^{2}}s} + 1}} \\{= \frac{\frac{a^{2}A_{p}}{V_{2}L_{p}}}{s^{2} + {\frac{{RV}_{2}}{a^{2}}\frac{a^{2}A_{p}}{V_{2}L_{p}}s} + \frac{a^{2}A_{p}}{V_{2}L_{p}}}} \\{= {\frac{\omega_{n}^{2}}{s^{2} + {\frac{{RA}_{p}}{L_{p}}s} + \omega_{n}^{2}}.}}\end{matrix}$

In either of the foregoing cases, the resonant frequency of the systemmay be expressed as a function of the variable volume, V₂:

${\omega_{n}^{2} = {\frac{a^{2}A}{L}\left( {\frac{1}{V_{1}} + \frac{1}{V_{2}}} \right)}},{{{or}\mspace{14mu}\frac{1}{V_{2}}} = {\frac{\omega_{n}^{2}L}{a^{2}A} - {\frac{1}{V_{1}}.}}}$

Since all of the other parameters are known, variable volume V₂ can becalculated based, for example, on the resonant frequency, although othermethods of deriving V₂ may be advantageous, and are described further inthe course of the present application. The one parameter that is not aconstant in this equation is the speed of sound, a, which may becalculated, based on a knowledge of the pertinent temperature, orotherwise derived or measured.

As stated, various strategies may be employed to interrogate the systemso as to derive volume V₂. In accordance with certain embodiments of thecurrent invention, the system is excited by driving member 1214 at asingle frequency, while monitoring the response of one or moretransducers (microphones 1208 and 1209, in FIG. 9). The response iscaptured as a complex signal, retaining both amplitude and phase of thepressure variation. It is advantageous that the single interrogatingfrequency lie close to the resonance of the system in mid-stroke, sincethe largest phase changes with volume over the range of a full to emptychamber is thereby achieved.

The response of the signal microphone 1208 may be corrected to rejectcommon-mode effects due to the frequency-dependent characteristics ofthe exciting loudspeaker 1202 (shown in FIG. 6) or driving member 1214(shown in FIG. 9). The corrected signal, obtained as a complex ratio ofthe microphone signals, may be expressed as m_(i), where the index idenotes successive time samples of the signal.

Expressed, in transfer function form, in analogy, to a second-ordermechanical Helmholtz resonator, the signal may be represented as:

$\begin{matrix}{m_{i} \approx {{- \frac{V_{0}}{V_{1}}}\frac{\frac{A\;\gamma\;{RT}}{{LV}_{2}}}{s_{i}^{2} + {\frac{\lambda\; A}{L}s_{i}} + {\frac{A\;\gamma\;{RT}}{{LV}_{2}} \cdot \frac{V_{1} + V_{2}}{V_{1}}}}}} \\{= \frac{{- \frac{V_{0}}{V_{1}}} \cdot \frac{A\;\gamma\; R}{L\;\omega_{c}^{2}} \cdot \frac{T_{i}}{V_{2\;}} \cdot \frac{\alpha}{ɛ_{v,i}}}{\frac{s_{i}^{2}}{\omega_{c}^{2}} + {\frac{A\;\lambda}{L\;\omega_{c}} \cdot ɛ_{\lambda} \cdot \frac{s_{i}}{\omega_{c}}} + {\frac{A\;\gamma\; R}{L\;\omega_{c}^{2}} \cdot \frac{T_{i}}{V_{1}} \cdot \frac{\left( {ɛ_{v,i} + \Psi_{1,2}} \right)}{ɛ_{v,i}}}}} \\{= \frac{{- \kappa_{0,i}}\;\frac{\alpha}{ɛ_{v,i}}}{{\overset{\_}{s}}_{i}^{2} + {\psi_{1} \cdot {\overset{\_}{s}}_{i} \cdot ɛ_{\lambda}} + {\psi_{0,i}\frac{\Psi_{1,2} + ɛ_{v,i}}{ɛ_{v,i}}}}} \\{= \frac{{- \kappa_{0,i}}\alpha}{{{\overset{\_}{s}}_{i}^{2}ɛ_{v,i}} + {\psi_{1}{\overset{\_}{s}}_{i}ɛ_{\lambda}ɛ_{v,i}} + {\psi_{0,i}\left( {\Psi_{1,2} + ɛ_{v,i}} \right)}}} \\{= {\frac{{- \kappa_{0,i}}\alpha}{\left\lbrack {{\psi_{0,i}\left( {\Psi_{1,2} + ɛ_{v,i}} \right)} - {{\overset{\_}{\omega}}_{i}^{2}ɛ_{v,i}}} \right\rbrack + {{\iota \cdot \psi_{1}}{\overset{\_}{\omega}}_{i}ɛ_{\lambda}ɛ_{v,i}}} \cdot}} \\{\frac{\left\lbrack {{\psi_{0,i}\left( {\Psi_{1,2} + ɛ_{v,i}} \right)} - {{\overset{\_}{\omega}}_{i}^{2}ɛ_{v,i}}} \right\rbrack - {{\iota \cdot \psi_{1}}{\overset{\_}{\omega}}_{i}ɛ_{\lambda}ɛ_{v,i}}}{\left\lbrack {{\psi_{0,i}\left( {\Psi_{1,2} + ɛ_{v,i}} \right)} - {{\overset{\_}{\omega}}_{i}^{2}ɛ_{v,i}}} \right\rbrack - {{\iota \cdot \psi_{1}}{\overset{\_}{\omega}}_{i}ɛ_{\lambda}ɛ_{v,i}}}} \\{= \frac{{{- \kappa_{0,i}}{\alpha\left\lbrack {{\psi_{0,i}\Psi_{1,2}} + {\left( {\psi_{0,i} - {\overset{\_}{\omega}}_{i}^{2}} \right)ɛ_{v,i}}} \right\rbrack}} + {{\iota \cdot \kappa_{0,i}}\alpha\;\psi_{1}{\overset{\_}{\omega}}_{i}ɛ_{\lambda}ɛ_{v,i}}}{\left\lbrack {{\psi_{0,i}\Psi_{1,2}} + {\left( {\psi_{0,i} - {\overset{\_}{\omega}}_{i}^{2}} \right)ɛ_{v,i}}} \right\rbrack^{2} + {\psi_{1}^{2}{\overset{\_}{\omega}}_{i}^{2}ɛ_{\lambda}^{2}ɛ_{v,i}^{2}}}}\end{matrix}$

Here, normalization variables have been introduced so as to maintainrelevant parameters within a computationally useful dynamic range oforder unity. The final expression is expressed in terms of the real andimaginary parts over a common denominator. Taking the ratio of the realμ to the imaginary v parts, (i.e., the phase cotangent),

${\frac{\mu_{i}}{v_{i}} \approx {- \frac{{\left( {\psi_{0,i} - {\overset{\_}{\omega}}_{i}^{2}} \right)ɛ_{v,i}} + {\psi_{0,i}\Psi_{1,2}}}{\psi_{1}{\overset{\_}{\omega}}_{i}ɛ_{\lambda}ɛ_{v,i}}}},$the error may be defined as:

${E = {\frac{1}{M}{\sum\left\lbrack {{\mu_{i}D_{i}} + {v_{i}N_{i}}} \right\rbrack^{2}}}},$with N and D denoting the numerator and denominator, respectively of themodel.

If the error is minimized with respect to each of the model parameters,a best-fit has been achieved. Any method may be employed for fitting themodel parameters. In one embodiment of the invention, a gradient-descentmethod is employed to find the minima:

$\mspace{20mu}{\frac{\partial E}{\partial ɛ_{\lambda}} = {\frac{2}{M}{\sum{\psi_{1}{\overset{\_}{\omega}}_{i}ɛ_{v,i}D_{i}e_{i}}}}}$$\frac{\partial E}{\partial ɛ_{b\;}} = {{\frac{2}{M}{\sum{\left( {{\mu_{i}\frac{\partial D_{i}}{\partial ɛ_{b}}} + {v_{i}\frac{\partial N_{i}}{\partial ɛ_{b}}}} \right)e_{i}}}} = {2{\sum{\left( {{\mu_{i}\frac{\partial D_{i}}{\partial ɛ_{v,i}}} + {v_{i}\frac{\partial N_{i}}{\partial ɛ_{v,i}}}} \right)e_{i}\frac{\partial ɛ_{v,i}}{\partial ɛ_{b\;}}}}}}$$\mspace{20mu}{\frac{\partial D_{i}}{\partial ɛ_{v,i}} = {\psi_{1}{\overset{\_}{\omega}}_{i}ɛ_{\lambda}}}$$\mspace{20mu}{\frac{\partial N_{i}}{\partial ɛ_{v,i}} = {\psi_{0,i} - {\overset{\_}{\omega}}_{i}^{2}}}$$\mspace{20mu}{\frac{\partial ɛ_{v,i}}{\partial ɛ_{b}} = 1}$$\mspace{20mu}{\frac{\partial E}{\partial\delta_{d}} = {\frac{2}{M}{\sum{\left( {{\mu_{i}\frac{\partial D_{i}}{\partial ɛ_{v,i}}} + {v_{i}\frac{\partial N_{i}}{\partial ɛ_{v,i}}}} \right)e_{i}\frac{\partial ɛ_{v,i}}{\partial\delta_{d}}}}}}$$\mspace{20mu}{\frac{\partial ɛ_{v,i}}{\partial\delta_{d}} = {\exp\left( {{- t_{i}}{ɛ_{\tau}/\tau}} \right)}}$$\mspace{20mu}{\frac{\partial E}{\partial ɛ_{\tau}} = {\frac{2}{M}{\sum{\left( {{\mu_{i}\frac{\partial D_{i}}{\partial ɛ_{v,i}}} + {v_{i}\frac{\partial N_{i}}{\partial ɛ_{v,i}}}} \right)e_{i}\frac{\partial ɛ_{v,i}}{\partial ɛ_{\tau\;}}}}}}$$\mspace{20mu}{\frac{\partial ɛ_{v,i}}{\partial ɛ_{\tau}} = {\delta_{d}\frac{- t_{i}}{\tau}{{\exp\left( {{- t_{i}}{ɛ_{\tau}/\tau}} \right)}.}}}$

The intervals over which each successive temporal sample is obtained,and the number of intervals sampled in order to fit the parameters ofthe temporal model are advantageously optimized for each specificapplication of the invention. Where fluid flows at a slow but relativelyconstant rate, as in basal insulin delivery, sampling over a period fromτ/3 to 3τ has been found efficacious. On the other extreme, where arelatively large bolus of fluid is to be delivered, the fluid may residein dispensing volume 122 for only a short period of time, on the timescale of the exponential decay time constant. In that case, sampling isperformed over a shorter fraction of the characteristic decay time.

In accordance with preferred embodiments of the invention, volume offluid dispensed through dispensing volume 122 is determined on the basisof a fit to a model of volume vs. time, based on cross-system phasemeasurements made at monotonic frequency of excitation. During theinitial portion of a pump stroke, moreover, preliminary measurements aremade in order to calibrate system operation, as now described, inconjunction with the measurement protocol, with reference to theflowchart shown in FIG. 117. The metering process, denoted generally bynumeral 1170, advantageously conserves computer resources and minimizespower consumption, thereby extending the useful time between charges orreplacement of power source 1211 (shown in FIG. 9), while providing,through frequent calibration, the measurement accuracy required fordelivery of fluid with the resolution per stroke described above.

Either prior to, or at the beginning 1171 of, each pump stroke, or both,processor 1210 initiates a Self-Calibration Phase 1172 of the AVSsystem. Measurements are held-off until electronic transients due toactivation of the pump have substantially decayed. Microphone andspeaker gains are set, and driving member 1214 is actuated, in step1173, at a succession of frequencies, where typically five frequenciesare employed, in the general proximity of the resonance of contiguousacoustic region 1290 (otherwise referred to herein as the “acousticchamber”). Frequencies in the range of 6-8 kHz are typically employed,though the use of any frequencies is within the scope of the presentinvention. At the onset of activation of each successive frequency, datacollection is delayed, for a period of approximately 5 ms, untilacoustic transients have substantially decayed.

For a duration of approximately 64 acoustic cycles, data are collectedas follows: the temperature reading provided by temperature sensor 132(shown in FIG. 70B) is sampled in step 1174, and the real and imaginaryportions of the ratio of output signals of signal microphone 1209 withrespect to reference microphone 1208, denoted ρ and ι, respectively, aresampled. The complex ratio of signals, or other functional combinationof the microphone signals with respect to the reference, may be referredto herein as the “signal,” for purposes of describing the AVS system.

On the basis of measurements at each frequency, taken over the course ofapproximately 200 ms per frequency, a set of means and variances arederived for each of the real and imaginary parts of the signal at eachfrequency and for the temperature readings. Analysis, in step 1175, ofthese values, permits a determination of whether errors are withinspecified bounds. An anomalous transfer function may advantageouslyindicate system faults that include, but are not limited to, faults inthe microphones or other sensors, speaker, transducer, electronics,mechanical components, fluid ingress, poor acoustic seal, excessiveambient noise, and excessive shock and vibration. Additionally, thefunctional dependence of the phase angle of the signal as a function offrequency is determined in step 1176. The phase angle of the signal,namely the arctangent of the ratio of imaginary to real portionsthereof, may be used as a measure of phase, however any measure of phasemay be used within the scope of the invention. The functional dependencemay be derived by polynomial fit of the phase to the frequency, orotherwise. On the basis of the polynomial fit, or otherwise, the slopeof phase vs. frequency is determined at the volume measurementfrequency, and volume measurement proceeds, in step 1177. Additionally,and significantly, an anomalous slope of phase vs. frequency isindicative of a gaseous bubble in the fluid contained within dispensingchamber 122.

For a succeeding portion of each pump stroke, driving member 1214 isactuated at substantially a single frequency, thereby acousticallyexciting the gas within acoustically contiguous region 1290 at thatfrequency. Signal data, based typically on the complex ratio of outputsignals of signal microphone 1209 with respect to reference microphone1208 are collected and averaged over specified sampling intervals ofapproximately 64 cycles. Real and imaginary components of the signal, aswell as temperature data, are recorded for each sampling interval. Basedon the sampled and collected data, a fit is performed to a temporalmodel. In various embodiments of the invention, a gradient-descentmethod is employed, as described above, in order to minimize error infitting the model parameters, namely the baseline volume V_(B), peakdisplacement V_(D), and decay time τ, of the variable volume chamber 121during the course of each pump stroke, thereby providing the volume offluid delivered through dispensing chamber 122.

Referring now to FIG. 10, the dispensing spring 130 may have a spiral orfan shape that is complementary to the diaphragm and may have multiplehelical grooves 131. Embodiments of the spring as shown can apply anapproximately even force over the diaphragm. This approximately evenforce helps the diaphragm to retain an approximately concave shape as itexpands. The grooves 131 allow air to pass freely through the spring,thus most air is not trapped between the spring and the diaphragm.

Referring now to FIGS. 11A and 11B, examples of kinetic measurements ofthe volume of the dispensing chamber 122 (shown in FIG. 5) and of thecalculated cumulative volume expelled from the dispensing chamber 122are shown for a typical basal delivery pulse (FIG. 11A) and for atypical bolus delivery (FIG. 11B). As can be seen in FIG. 11A, actuationof the pumping assembly 16 causes an expansion of the dispensing chamber122, as measured by the acoustic volume sensor 550, from about 0 toabout 1.5 μl in about 2 seconds. The resilient dispensing chamber 122 isseen to contract and expel its fluid from the chamber 122 through thehigh impedance output over a course of about 30 seconds with anexponential decay kinetic characterized by a half-life (t_(1/2)) ofabout 6 seconds. The cumulative volume of output from dispensing chamber122 is calculated from the measurements made by the sensor 550 and seenalso to rise exponentially to about 1.5 μl. It can be seen that the highimpedance output introduces a delay between actuation of the pumpassembly and delivery of the majority of the displaced fluid. Thet_(1/2) characteristic of the system can be chosen with attention to theresilient force exerted by the dispensing chamber 122 and the degree ofimpedance of the output. In various embodiments, the time constant mayvary to save power and eliminate drift issues. The time constant may be,for example, t_(1/2)=2 seconds, or t_(1/e)=2 seconds.

FIG. 11B shows a kinetic profile of a bolus delivery of fluid by thefluid delivery device 10. A rapid succession of about 29 pump actuations(i.e., pulses) each displace fluid from a fluid source into theresilient dispensing chamber 122, thus causing corresponding changes inthe parameter measured by the acoustic volume measurement sensor 550. Itcan be seen that the volume of the dispensing chamber 122 expands on thefirst pump pulse to about 1.5 μl, a value similar to that observed inFIG. 11A. The dispensing chamber 122 volume further expands uponadditional pulsatile pumping at pulse intervals shorter than the timeperiod required to achieve full discharge of the dispensing assembly120; the expansion reaches a maximum of about 6 μl. Cessation of thepump pulsing occurs after about 85 seconds and the volume of the chamber122 is seen to decrease with an exponential decay kinetic resulting incomplete discharge of its contents by about 30 seconds after cessationof pumping. The t_(1/2) for this final discharge is approximately thesame as for the basal delivery shown in FIG. 11A. The calculatedcumulative output volume is seen to rise during pumping with anapproximately linear kinetic and plateau upon cessation of pumping.

In the described system, fault conditions are detected by volumemeasurements rather than by pressure measurements, thus, faults may bedetermined in seconds. FIGS. 11C-11F illustrate the sensor 550 of FIGS.5-7 detection various types of fault conditions. All description withrespect to FIGS. 11C-11F are described with reference to FIGS. 5-7.

FIG. 11C shows a kinetic profile of sensor 550 output over time for apumping pulse under normal operating conditions. In contrast, FIG. 11Dshows an expected result of an occlusion downstream of the dispensingassembly 120; the increasing (or not decreasing) volume of fluid in thedispensing chamber 122 is quickly detected by the sensor 550.

Low volume conditions are shown in FIGS. 11E-11F. In FIG. 11E, anapproximate maximum sensor signal is reached, followed by an overly fastdecay; this condition may indicate an internal leak in the pump 16, line310, or dispensing assembly 120. The kinetic profile of FIG. 11F has alow peak volume signal and may be representative of a pump failure, anempty reservoir 20, or an occlusion that is upstream of the dispensingchamber 122. Delayed expansion of the dispensing chamber 122 in responseto pump actuation may also indicate a problem in the flow line 310. Thesensor 550 may also be capable of detecting bubbles in the fluid. Analarm can be activated in response to detection of a fault condition.

FIG. 12 shows a flow chart depicting a cycle of acoustic volume sensingand compensation (corresponding to control loop 360 of FIGS. 2A-3). Thesensor may measure the amount of fluid dispensed from the device 10based on measures of the magnitude of the cyclical changes in thevariable volume chamber 121 induced by the pumping cycles. For example,the sensor 550 may repeatedly acquire acoustic spectra of the resonantvariable volume 121 and the reference volume chamber 127 (step 2611) andmaintains a parameter, which, for each pumping pulse, is updated toincorporate the decrease in volume of gas in the variable volume chamber121. Accordingly the updated parameter indicates the net quantity offluid that has entered the dispensing chamber 122. The fluid enteringthe dispensing chamber 122 is approximately equal to the volume that hasbeen dispensed by the device 10 if there is sufficient delay betweenpulses. Alternately, the sensor 550 can repeatedly measure the increasein the volume of gas in the variable volume chamber 121 to determine theamount dispensed by the device (if there is a sufficient delay betweenpulses). Acoustic spectra are compared to model spectra in a lookuptable that may correspond to any or all of a dispensing chamber 122 witha bubble, without a bubble, or with bubbles of varying sizes (step2621). The lookup table may hold data acquired experimentally,determined using a model, or determined to work empirically. The lookuptable may contain data representing varying bubble containing and/ornormal conditions for multiple degrees of expansion of dispensingchamber 122. If the spectrum and updated sum fit a model of normal flow(step 2631), another acoustic spectrum is acquired and the cycle isrepeated at step 2611. If the spectrum and/or the updated sum do not fita model of normal flow, the presence of a low or occluded flow will bedetermined (step 2641). A low or occluded flow may be indicated by apersistently out-of-range volume of the variable volume chamber 121, byan updated sum that is lower than a predicted or set value, or both. Ifa low or occluded flow condition is detected, an alarm will be triggered(step 2671). Alarms may include audible signals, vibrations, or both. Ifno condition of low or occluded flow is found, the device determines ifthe spectrum fits a model corresponding to a condition of a bubble inthe dispensing chamber 122 (step 2661). If a bubble is determined to bepresent, a reaction is initiated that may include an alarm and/orcompensatory action which may include temporarily increasing the rate ofpumping (step 2651) and the cycle will begin again at step 2611. If itis determined that no bubble is present, an alarm is triggered toindicate an undetermined fault condition (step 2671). Embodiments of thepresent invention may also utilize bubble detection using AVS technologyas disclosed in U.S. Patent Application, Ser. No. 60/789,243, which isincorporated herein by reference.

The pumping assembly 16 of FIGS. 2A-3 urges fluid from the reservoir 20to the dispensing assembly 120. When a dispensing assembly according toFIGS. 6-7 is used, it is not necessary to use a high precision pump,because the feedback provided from the dispensing assembly 120 to thepumping assembly 16 allows adjustment of the pumping assembly 16 basedon exact measurements of the volume being delivered. The individualpumping pulses may be of sufficiently low volume to allow precisecompensation based on the feedback. Many different pumping assembly 16implementations can therefore be employed. Various possible embodimentsof the pumping assembly 16 are described below.

FIGS. 13 and 14 schematically show alternate embodiments of some of thecomponents in a fluid delivery device according to an embodiment of theinvention. FIG. 13 shows a flow line 310 with a pumping assembly 16having a pumping element 2100 located between an upstream one way valve21 and a downstream one way valve 22. The pumping element 2100 may usean actuator to deform a portion of the flow line to generate pressure inthe flow line 310. The upstream one way valve 21 inhibits retrogradeflow from the pumping element 2100 toward a fluid source (not shown),while the downstream one way valve 22 inhibits retrograde flow from thevolume-sensing chamber 120 to the pumping element 2100. As a result,fluid is driven in the direction of the exit assembly 17, which, in oneembodiment, includes a high-impedance passage.

In an alternate embodiment shown in FIG. 14, the functions of thepumping element, i.e., generating pressure in the flow line 310, and theupstream one way valve 21 are performed by a combined valving pump 2200.Thus, the pumping assembly 16 in the FIG. 14 embodiment is made up oftwo components—the combined valving pump 2200 and the downstream one wayvalve 22—instead of the three components used in the FIG. 13 embodiment.Other embodiments of the pumping assembly 16 may be used. Thecombination of valving and pumping functions in valving pump 2200 may beaccomplished by a variety of mechanisms, some of which are describedbelow with reference to FIGS. 15A-16 and 22-56.

In many of the embodiments described below, the poppet for the inletvalve 21, the poppet for the exit valve 22 and the pumping actuationmember 54 are all either directly or indirectly (e.g., as in FIGS.50-56) in communication with the fluid line 310 such that each of theseelements are able to create or react to various fluid pressures. Asnoted above, the upstream and downstream valves—which may also bereferred to herein as the inlet and exit valves—are one way valves. Thevalves can be volcano, flapper, check or duck-bill valves, amongst othertypes of one way valves, or other types of valves that bias the flowtoward the device output. An example of volcano valves are disclosed inU.S. Pat. No. 5,178,182 issued Jan. 12, 1993 to Dean L. Kamen, andincorporated herein by reference.

In the embodiment shown in FIGS. 15A-15D, the pumping assembly includesboth an inlet valve 21 and an exit valve 22, each of which includes afluid inlet, a fluid exit, and a moveable member (which is, for eachvalve, a portion of membrane 2356). The pumping assembly also includes apumping element 2100. The pumping element is located downstream from theinlet valve 21 and upstream from the exit valve 22. In the followingdescription, the exit valve will be starting from the closed position,i.e., fluid is not flowing through the exit valve. However, at a timewhen the fluid presents enough pressure, the fluid pressure opens theexit valve by placing pressure on the membrane and the exit valve'spoppet 9221 to open the valve, and the fluid can then flow through theexit valve 22. The embodiment of FIGS. 15 A through 15D may beconsidered to be a combined valving-pump (like item 2200 in FIG. 14), inthe sense that a single mechanical action both occludes a pump inlet andthen urges flow through a pump outlet.

This pumping arrangement has the advantage of partitioning the movingparts and wetted line components to opposite sides of a flexible barriermembrane 2356. As a result, the moving parts may be located in areusable component and the wetted parts (fluidic line 310) may belocated in a disposable component.

In a preferred embodiment of the pumping mechanism, the fluid source isa non-pressurized reservoir. When the moveable member of the inlet valveis in the open position, and a negative pressure exists in the pumpingchamber, a pressure differential exists that pulls the fluid from thereservoir towards the inlet valve. This negative pressure may be createdby the resiliency of the membrane in the pumping chamber. In onealternative embodiment, a spring—which may be built into themembrane—may be used to assist in the recoil of the membrane in thepumping chamber. The non-pressurized reservoir may be collapsible, sothat when fluid is drawn from it, a corresponding collapse in thereservoir reduces its volume. As a result, build-up of negativepressure, or air in the reservoir is prevented.

In a preferred embodiment of the pumping mechanism, after the inletvalve is closed, pressure is applied to the pumping chamber forcingfluid from the pumping chamber towards the exit valve. Pressure createdby the pumping motion opens the exit valve and allows fluid to flowthrough the exit valve's fluid exit.

The moveable member can be anything capable of functioning as describedabove. In some embodiments, the moveable member is a flexible membraneor a resilient pumping diaphragm. In other embodiments, the moveablemember is a ball-shaped rigid structure or another object capable ofpreventing fluid from flowing out of an opening in the fluid path.

In practice, the pumping mechanism may be primed prior to use. Thus, thepumping mechanism cycles through a number of strokes, purging air fromthe fluid line, until most or all of the air in the fluid line ispurged. Many of the pumping mechanisms disclosed herein have the abilityto “self-prime” because the fluid volume contained outside the pumpingchamber, but between the valves, is small. When the pump squeezes air inthe pump chamber, it generally builds up enough pressure to blow pastthe exit valve. The subsequent return stroke can therefore developsufficient negative pressure for the pump to pull liquid from thereservoir. If the “dead” volume of the pump is too large, the air in thepumping chamber may not build up enough pressure to escape the exitvalve. As a result, the pump may stall.

FIGS. 15A-15D, 16 and 22-56 show several embodiments of the pumpingmechanism. Referring now to FIGS. 15A-15D, one embodiment of the pumpingmechanism is shown exemplifying several steps in the pumping process: 1.fluid passing through the inlet valve 21 (as shown in FIG. 15B); 2. theinlet valve closed (as shown in FIG. 15C); and 3. the pumping actuationmember 54 forcing fluid downstream, with fluid pressure opening the exitvalve 22 and flowing through the fluid exit (as shown in FIG. 15D).

The pumping mechanism of FIGS. 15A-15D includes a moveable member,which, in this embodiment, is a portion of the flexible membrane 2356.The inlet and exit valves include poppets 9221, 9222 that function asvalve occluders. Each of the poppets 9221, 9222 and the pump actuationmember 54 include a spring 8002, 8004, 8006. The pump plate 8000 isattached to both the pump actuation member 54 and the inlet poppet 9221and serves as a terminus to their respective springs 8004, 8002.

The term “poppet” is used to denote a member that applies pressureagainst the moveable member (i.e., the membrane) to affect the positionof the membrane. Although other designs may be used, some specificexamples of spring-loaded poppet valves that utilize structures andprinciples of mechanical advantage are described below (in connectionwith FIGS. 50-56). However, mechanisms other than poppets can be used toperform the same function. In FIGS. 15B-15D, the inlet valve 21 includesa fluid inlet and fluid exit, part of the membrane 2356, and a poppet9221. The exit valve 22 includes a fluid inlet a fluid exit, part of themembrane and a poppet 9222.

In the embodiment shown in FIGS. 15A-15D, the fluid path 310 is definedby a structure (item 9310 in FIG. 15A), which may be rigid or have someflexibility (preferably less flexibility than membrane 2356. As shown inFIG. 15A, the housing structure 9310 defines the valving chambers 9321,9322 and the pumping chamber 2350; all three of these chambers are inthe fluid path 310.

Referring now to FIGS. 15B-15D, the inlet valve 21, exit valve 22 andpump element 2100 each have a fluid inlet and a fluid exit. The pumpingactuation member 54 has a pumping chamber 2350 where the fluid flowsafter exiting the inlet valve. Pumping actuation member 54 appliespressure onto the membrane 2356, creating positive pressure in the fluidline.

As shown in FIGS. 15B-15D (and similarly for the valve seat 4070 for theoutlet valve shown in FIGS. 50-56), the valve seat 9121 in the inletvalve 21 is preferably spaced away from the membrane 2356, when themembrane is not being actuated by the poppet 9221 of the inlet valve.

The fluid line 310 is partially defined by a membrane 2356. In thisembodiment, the membrane 2356 separates parts of the pumping mechanismfrom the fluid. Thus, the fluid line 310 is wetted and the pumpingactuator 54 and the valve poppets 9221, 9222 are not wetted. However,alternative embodiments of the pumping assembly do not need to include amembrane 2356 that is in contact with the fluid line 310. Instead, adifferent moveable member may be used for the valves and/or pump. Instill other embodiments, only parts of the fluid line 310 are separatedfrom the pumping mechanism, thus partially wetting the pumping assembly.

The inlet poppet 9221 includes an end 8018 referring to the surface areaof the inlet poppet that contacts the membrane portion of the fluid line310. The pumping actuation member 54 includes an end 8012 that contactsthe membrane portion of the fluid line 310. Likewise, the exit poppet 22includes an end 8022 that contacts the membrane portion of the fluidline 310. The ends 8018, 8022 of the valve poppets apply pressure ontotheir respective areas of the membrane 2356, blocking or unblocking therespective portions of the flow path 310. The end 8012 of the pressureactuation member also applies pressure onto its respective area of themembrane, so as to cause flow through the fluid line 310.

The pumping actuation member 54 is surrounded by a plunger biasingspring 8004. The plunger biasing spring 8004 has both a terminus at thepump plate 8000 and at 8014, a support structure that also holds thepumping actuation member.

The inlet poppet 21 is surrounded by an inlet poppet spring 8002,although in alternate embodiments, the inlet poppet itself is resilientand so serves the function of the spring. The inlet poppet spring 8002has both a terminus at the pump plate 8000 and near the end 8018 of theinlet poppet 9221.

The exit poppet 9222 is surrounded by a passive exit poppet spring 8006.The exit poppet spring 8006 has both a terminus at an exit poppet plate8024 and the lip 8020 near the end of the exit poppet 9222.

In each case, the springs 8002, 8004, 8006 terminate before therespective ends and do not interfere with the surface areas 8018, 8012,8022 that contact the membrane 2356.

In a preferred embodiment, the fluid pumping device also includes atleast one shape memory actuator 278 (e.g., a conductive shape-memoryalloy wire) that changes shape with temperature. The temperature of theshape-memory actuator(s) may be changed with a heater, or moreconveniently, by application of an electric current. FIGS. 15B-15D showan embodiment with one shape memory actuator 278, however, in otherembodiments (described below) there may be more than one shape memoryactuator 278. In one embodiment, the shape memory actuator is a shapememory wire constructed of nickel/titanium alloy, such as NITINOL™ orFLEXINOL®. However, in other embodiments, any device capable ofgenerating a force, such as a solenoid, could also be used. In certainembodiments, the shape memory actuator 278 has a diameter of about 0.003inches and is about 1.5 inches in length. However, in other embodiments,the shape memory actuator 278 may be made from any alloy capable ofcontraction with heat (and expansion may be aided by a mechanism thatimparts force on the alloy so as to stretch the alloy to the originallength, i.e., a spring, although such a mechanism is not required) so asto actuate the pumping mechanism as described in the embodiments herein.In certain embodiments, the diameter of the shape memory actuator 278can be from 0.001 inches to any diameter desired and the length can beany length desired. Generally speaking, the larger the diameter, thehigher the available contraction force. However, the electrical currentrequired to heat the wire generally increases with diameter. Thus, thediameter, length and composition of the shape memory alloy 278 mayaffect the current necessary to actuate the pumping mechanism.Irrespective of the length of the shape memory actuator 278, theactuation force is approximately constant. Increase in actuation forcecan be imparted by increasing the diameter of the shape memory actuator278.

The shape memory actuator 278 connects to the pump plate 8000 throughconnector 8008. Connector 8008 is described in more detail below. Theshape memory actuator 278 connects to a fluid pumping device by way ofterminus connector 8010. Depending on the device or system in which thepumping mechanism is used, the terminus connection location will vary.The terminus connector 8010 is described in more detail below.

FIGS. 15B-15D show the pumping mechanism and fluid line 310 havingalready been primed as discussed above. Referring now to FIG. 15B, theinlet valve 21 is open, and the pumping actuation member 54 is notpressing against the membrane 2356. The exit valve 22 is in the closedposition. The shape memory actuator 278 is in an expanded position. Inthis configuration, fluid is pulled from a reservoir (not shown) to theinlet valve 21 fluid inlet. (Although shown as a bulge in the membranein the inlet valve region, the pulling of fluid in this step may cause adepression in the membrane, or no deformation of the membrane). When theinlet poppet is in the open position, the fluid can flow from the fluidinlet to the fluid exit and into the pumping chamber 2350. At thispoint, the exit poppet end 8022 is firmly pressed against the membrane2356 and seals the exit valve 22.

Referring next to FIG. 15C, electrical current has been applied to theshape memory actuator 278, and the shape memory actuator is contractingfrom a starting length towards the desired end length. The contractingof the shape memory actuator 278 pulls the pump plate 8000 towards thefluid line 310. The inlet poppet 9221 and the pumping actuation member54 are both connected to the pumping plate 8000. The motion of the plate8000 pulls both the inlet poppet 9221 and pumping actuation member 54towards the membrane 2356. As shown in FIG. 15C, the inlet poppet end8018 is pressed firmly against the membrane 2356, sealing the membraneagainst the valve seat 9121 and, closing the inlet valve 21. (The motionof the inlet poppet can force a small amount of fluid in the inletvalving chamber, item 9321 in FIG. 15A, through either the fluid inletor the fluid exit of the inlet valve 21.)

Simultaneously, the pumping actuation member 54 begins its path towardsthe pumping chamber 2350. During this process, as the inlet poppetspring 8002 is compressed (at this point, the inlet poppet end 8018 ispressing firmly against the fluid line 310), the pump plate 8000 andpumping actuation member 54 continue traveling towards the fluid line310. The inlet poppet spring 8002 allows the pump plate 8000 to continuemoving toward the fluid line 310 with the pump actuation member 54 evenwhen the inlet poppet 9221 can not travel any further.

Referring now to FIG. 15D, the pumping actuation member 54 pressesagainst the area of the membrane 2356 over the pumping chamber 2350 andthe fluid is pumped so as to increase the pressure of the fluid in thepumping chamber 2350. The exit poppet end 8022 remains pressing firmly(aided by the exit poppet spring 8006) on the membrane 2356 sealing thefluid inlet and fluid exit of the exit valve 22 until the pressure fromthe fluid flowing from the pumping chamber 2350 forces exit valve 22open. Upon reaching a sufficient pressure, the fluid exits through thefluid exit of the exit valve 22, thus overcoming the pressure exertedagainst the membrane 2356 by the exit valve 22. Upon cessation of flow,the exit valve 22 is forced closed by the passive spring 8006.

During the work stroke, the pump actuation member spring 8004 is loaded.Eventually, the pump actuation member spring 8004 will pull the pumpactuation member 54 away from the membrane 2356. As a result, during therelaxation stroke, the spring 8004 returns the pump actuation member 54,and pumping plate 8000 to the relaxed position of FIG. 15C; the loadedinlet poppet spring 8002 may also contribute energy to the returnstroke. As the pumping plate 8000 nears its relaxed position, it engagesa cap of the inlet poppet 9221 to lift and unseat the inlet poppet so asto open the inlet valve 21. The pump actuation member spring 8004 alsounloads during the return stroke.

The pump plate 8000, reaching a threshold distance where the inletpoppet spring 8002 is at the same level as the pump plate 8000, willunload with the pump actuation member spring 8004. The membrane 2356 inthe pumping chamber 2350, being resilient, will return to its startingposition. This creates a negative pressure and as the inlet valve opens,fluid will flow through the inlet valve's fluid inlet to the fluid exitand towards the pumping chamber 2350. Thus, the pumping mechanism willnow be in the state as shown in FIG. 15B.

The entire pump sequence described with respect to FIGS. 15B-15D willrepeat each time the pump is actuated through application of currentonto the shape memory actuator 278.

The membranes referred to herein, including membrane 2356, may be madefrom any resilient material capable of imparting the necessarycharacteristics to function as described herein. Additionally, themembrane material may include a biocompatible material so as not toimpede operation of the pump or diminish the therapeutic value of thefluid. Multiple biocompatible resilient materials may be suitable,including nitrile and silicone. However, different therapeutic fluidcompositions may require different choices of resilient material.

The pumping mechanism described above and also various embodiments asdescribed herein can be described in terms of stroke length. One way todetermine stroke length is by the total change in the length of theshape memory actuator during one cycle of contraction and expansion ofthe shape memory actuator. This difference will determine the totaldistance the pump rod travels and thus, the total amount of fluid thatflows out of the inlet chamber 2354 to the pumping chamber 2350, to theexit chamber 2352 and finally, out the exit chamber 2352. Another way todetermine stroke length is the travel distance of the pump plate 8000.For a partial stroke, the pump plate 8000 will not reach its maximumtravel distance. In one embodiment, very small or micro-strokes areinitiated continuously, pumping micro-liter volumes of fluid on acontinuous or regular basis, from the reservoir to the exit. Forexample, a micro-stroke may displace less than 20%, 10% or 1% of thevolume of the pumping chamber 2350.

FIG. 16 shows a variation of the pumping mechanism embodiment shown inFIG. 15B. In FIG. 16, two different shape memory actuators—a longer oneand a shorter one—are used. FIG. 16 shows an embodiment of the pumpingmechanism shown in FIG. 15B in which the shape memory wire 278 istensioned around a pulley 286 and splits into longer and shorterstrands. A common juncture serving as a negative terminal may be locatedwhere the longer and shorter strands split off. Completion of a circuitwith either or both of the alternate paths allows adjustment of thepumping force and/or stroke length. In an alternative embodiment, apiece of material, such as Kevlar material, extends from the commonjunction around the pulley to the force plate 8000, while two separatepieces of shape memory wire extend from the common junction to theirrespective supports. These embodiments provide both a pumping mode andan air purging mode, as described below, by using two wires withdifferent lengths.

With respect to varying stroke using the shape memory actuatorvariables, for a given length of shape memory actuator, the stroke isdependent on a number of variables: 1. total time electricity/heat isapplied; 2. total voltage of the electricity; and 3. the diameter of theshape memory actuator. Some variable embodiments are shown in FIGS.17-19. However, in some embodiments, the stroke can be varied whilemaintaining the length, electricity time and voltage. These embodimentsinclude multiple shape memory actuators (see FIG. 19) and multipleswitches on a single shape memory wire (see FIG. 17). As discussedabove, the desired stroke length can also be attained by modifying anyone or more of the variables.

Additionally, the timing of the application of heat or electric currentto the shape memory actuation can vary to control the stroke. Each timethe shape memory actuator is heated can be termed a pulse. Factors suchas the pulse frequency, pulse duration, and stroke length may affect theamount of fluid delivered over time.

FIGS. 17-19 additionally depict embodiments of pumping assemblies whichhave both a fluid pumping mode and an air purging mode. When activated,the air purging mode applies a compression stroke of increaseddisplacement and/or increased application of force by a forceapplication member. The air purging mode may be activated based on thelikelihood or knowledge of air being present in the pumping assembly.For example, the air purging mode may be activated when the line isattached to a reservoir, when a bubble is detected by a sensor orsensing apparatus, or when insufficient flow is detected by a sensor orsensing apparatus. Alternately, the two modes may be used to selectbetween displacing a smaller and a larger volume of fluid for a givenpumping pulse.

Referring now to FIG. 17, a schematic shows a pumping assembly actuatedby a shape memory actuator 278 and having multiple modes of operation.When a pumping chamber 2350 is filled with fluid, the pumping assemblyoperates in a fluid pumping mode. During fluid pumping mode, electricalcurrent flows between a negative electrical lead 2960 and a positiveelectrical lead 2961, causing resistive heating of the alloy shapememory actuator 278 and a resultant phase change and power stroke. Inone embodiment, during priming of the pumping mechanism or when a bubble2950 is suspected to be in the pumping chamber 2350, the air purgingmode is activated and electrical current flows along a path of extendedlength between a negative electrical lead 2960 and a positive electricallead 2965; the result is a compression stroke of greater force on anddisplacement of force application member 2320 which should be sufficientto displace air 2950 from the pumping chamber 2350 to the pump outlet2370. In alternate embodiments, the positive and negative leads may bereversed.

Referring now to FIG. 18, a schematic shows an alternate pumpingassembly having a plurality of shape memory actuators 278 having thesame length. The additional actuators may be used to increase theactuating pressure on the pumping chamber 2350, for example, to removean occlusion or air bubble in the fluid line, pumping chamber or otherarea of the pumping mechanism. The additional actuators may also providea redundancy to any pumping device. A single shape memory actuator maybe capable of imparting sufficient force to remove an air-bubble fromthe pumping chamber. Additionally, in the embodiment shown in FIG. 18,an additional return spring may be necessary depending on the length ofthe second shape memory actuator.

When a reservoir is first attached to a flow line having a pumpingassembly, the pumping mechanism (item 16 in FIGS. 13-14) is typicallyfilled with air. Air can also enter the pumping mechanism during normaloperation for various reasons. Since air is more compressible thanfluid, application of a compression stroke of a length that issufficient to displace a fluid may be insufficient to generate enoughpressure to overcome the cracking pressure of a one way valve of thepumping mechanism if there is a substantial amount of air in the fluidline. Accordingly, the pumping mechanism may stall. However, it may bedesired to force air through the line during priming or when aninnocuously small amount of air is present in the pumping assembly.Thus, the embodiments shown in FIG. 18 can be used to impart additionalforce in this situation.

FIG. 19 schematically shows an alternative pumping assembly 16 having aplurality of shape memory actuators. A first, shorter, shape memoryactuator 2975 has a first electrical lead 2976 and a second electricallead 2977. The shorter actuator 2975 is capable of generatingcompression strokes that are sufficient to displace fluid in the pumpingchamber 2350; the shorter shape memory alloy actuator 2975 is usedduring normal fluid pumping mode operations. When an air purging mode isindicated, or a larger pumped fluid volume is required, a second longershape memory alloy actuator 2970 may be used by sending a current alongan actuator length disposed between a first electrical lead 2973 and asecond electrical lead 2972. The longer shape memory alloy actuator 2970may also be used as a backup actuator for fluid pumping mode operationby creating a shorter circuit which includes an electrical path betweena first electrical lead 2972 and a second electrical lead 2971. Theshorter shape memory actuator 2975 may also be used to vary the strokevolume to provide better control at lower fluid volume rates. Themultiple mode actuators of FIGS. 17-19 are not limited to use with thepump components shown and may be employed with any of the variousembodiments of pumping mechanisms described herein including those usingfluid pumping devices as described below and those employing valvingpumps as described below. Thus, the desired stroke length can beinitiated by applying electricity/heat to the length shape memoryactuator that will provide the desired stroke length.

Referring now to FIGS. 20A and 20B, each shows one embodiment forattaching the shape memory actuator. These various embodiments can beused in any of the mechanisms or devices described herein which employ ashape memory actuator 278. Referring to both FIG. 20A and FIG. 20B, theshape memory actuator 278 is fed into a grommet 280. The grommet 280 isthen attached to a part 284. Although only two embodiments of this modeof attachment are shown, various other modes are used in otherembodiments. Other modes of attaching a grommet to a part or any fixedlocation can be used.

Referring now to FIGS. 21A and 21B, two exemplary embodiments ofattaching the shape memory actuator 278 for use with a pumping mechanism16 are shown. In each of these embodiments, the shape memory actuator278 is designed to turn around a pulley 286. Referring to FIG. 21A, theshape memory actuator 278 is attached to a piece 288, preferably made ofKEVLAR material, by way of grommet 280. One end of the shape memoryactuator 278 is shown attached to a part 284 by way of a set screwattachment 289. Referring now to FIG. 21B, one end of the shape memoryactuator is shown attached to a part 284 by a grommet 280.

Various embodiments of the pumping mechanism are shown in herein. Thepumping mechanisms may include an inlet valve, a pumping actuationmember and an exit valve. As discussed above, different types of one wayvalves may be used in alternative embodiments. Although the schematicshown in FIGS. 15A-15D shows one embodiment, the following figures showalternate embodiments.

Referring now to FIG. 22 and FIG. 23, a side view and a cross section ofa section of a pumping mechanism is shown. In this embodiment, thepumping actuation member is a pumping elongate finger 32. When force isexerted onto the finger 32, the finger 32 depresses the moveable memberand reduces the internal volume of the fluid line. The section of thepumping mechanism in FIGS. 22 and 23 shows only the pumping chamber.When combined with one way valves (items 21 and 22 of FIG. 13),application of a deforming force to moveable member 23 urges fluid toflow toward an exit assembly (not shown). As shown in FIGS. 22 and 23,the finger 32 is pointed for focusing of force, but in otherembodiments, the finger 32 may be flat, or of any other suitable shape.A spring 31 serves to bias the finger 32 toward a retracted positionwith respect to the resilient member 23 so that the finger 32 returns tothe retracted, non depressing position in the absence of application offorce. As shown in FIG. 23, a motor can be used to apply force onto thefinger 23. However, in other embodiments, a shape memory actuator isused. Various types of motors will be suitable including electric motorsand piezoelectric motors.

Referring to both FIGS. 22 and 23, a backstop 33 limits the potentialtravel of the finger 32, supports the moveable member 23, and ensures areduction of volume in the fluid line or pumping chamber by preventingthe moveable member 23 from moving out of position in response toapplication of force by the finger 32. As seen in FIG. 22, the backstop33 may advantageously have a shape complementary to the resilient member23. In various embodiments, the pumping assembly 16 may include a leveror crank driven on one end by a motor, compressing the resilient member23 at another end.

Referring now to FIG. 24, another embodiment of the pumping actuationmember is shown in relation to one section of the pumping assembly. Amotor or shape memory actuator (not shown) applies a rotating force to agrouping of coupled projections 42. These projects 42 serve as thepumping actuation member and, in turn, apply force to the moveablemember 23 in turn. Accordingly, intermittent pulses of force are appliedto the moveable member 23. The backstop 33, as shown, can travel withina housing 44 and is upwardly biased toward the resilient member 23 by aspring 46.

Referring now to FIG. 25, an embodiment of a force application assemblywith a pumping actuation member (here, a plunger) 54 inside a barrel 52is shown. A motor causes the plunger 54 to be alternately withdrawn andinserted into the barrel. When the plunger 54 is withdrawn, a negativepressure draws fluid from the reservoir (not shown) into a channel 51and a lumen 56. When the plunger 54 is inserted, the increased pressurein combination with the one way valves (not shown) drives fluid towardsthe dispensing assembly (not shown). The lumen 56 is connected to thechannel 51 via a connecting channel 58 and the volume of the barrellumen 56 decreases with the plunging action of the plunger 54 therebyurging fluid through the flow line 310.

FIGS. 26 and 27 show another embodiment where the pumping actuationmember is a plunger 54. A force application assembly and a linearactuator, that includes a shape memory actuation 278, drive the plunger54. In FIG. 26, a shape memory wire 278 is in a cool, expanded state andis attached to a first support 241 and a plunger attachment cap 244. Thecap 244 is in turn attached to a biasing spring 243 which is in turnattached to a second support 242. When the wire 278 is in an expandedstate, the biasing spring 243 is in a relaxed state. FIG. 27 shows theshape memory actuator 278 in a contracted state due to application of anelectric current to the wire 278 and coincident heating. Uponcontraction, a force is exerted on the cap 244 causing an insertingmovement of a plunger 54 and a corresponding pumping action. In thecontracted state, the biasing spring 243 is in a high potential energystate. Upon cessation of application of the electric field, the Nitinolwire 278 cools and expands again, allowing the biasing spring 243 toreturn the plunger 54 to its retracted state. As shown in FIG. 21A-21B,a shape memory actuator 278 may be wound around one or more pulleys.

FIGS. 28-30 show a variety of embodiments in which pumping isaccomplished by a pumping actuation member 54 using a shape memoryactuator 278 to compress a moveable member forming a pumping chamber.The pumping chamber is bounded by one way valves 21, 22. FIG. 28 showsan embodiment including a pumping mechanism where the pumping actuationmember is a plunger 54 in a barrel 52. The mechanism also includes alever 273, a fulcrum 274, and a shape memory actuator 278. A shapememory actuator 278 is held within a housing 298 and is attached at oneend to a conductive support 279 and at the other end to a positiveterminal 275 of a lever 273. The lever 273 is in turn attached at itscenter to a fulcrum 274 and at a second end to a plunger 54. An electriccurrent is applied to cause current to flow through the terminal 275,the shape memory actuator 278, and the conductive support 279, therebycausing the shape memory actuator 278 to contract, causing lever 273 topivot about the fulcrum 274 and effect withdrawal of the plunger 54.Cessation of the current allows cooling of the shape memory actuator278, allowing it to expand. The return spring 276 acts via the lever 273to return the plunger 54 to an inserted position within the barrel 52.The return spring 276 is held in a housing 277. An o-ring 281 preventsleaking of fluid from the plunger 54-barrel 52 assembly. The insertionand withdrawal of plunger 54 causes fluid to flow through the flow linein a direction determined by the orientation of two check valves: afirst one way valve 21 and a second one way valve 22. Any suitablebackflow prevention device may be used, which include one way valve,check valves, duck bill valves, flapper valves, and volcano valves.

FIG. 29 shows another embodiment of a pumping mechanism having a plunger54, a barrel 52, and a force application assembly that includes a shapememory actuator 278. However, this embodiment, unlike the embodimentshown in FIG. 28, does not include a lever. A shape memory actuator 278is held within a housing 298 and is attached at one end to a conductivesupport 279 and at the other end to a plunger cap 244 by way of contact275. The plunger cap 244 is attached to the plunger 54. Once ampleelectric current is applied through a contact 275, the shape memoryactuator 278 contracts. This contraction causes a pulling on the plungercap 244 to effect insertion of the plunger 54 into the barrel 52.Cessation of the current allows cooling and of the shape memory actuator278, thereby allowing it to expand. Upon expansion of the wire, thereturn spring 276 acts to return the plunger 54 to a withdrawn positionwithin the barrel 52. The return spring 276 is held in a housing 277.O-rings 281 prevent fluid from leaking plunger 54-barrel 52 assembly.The insertion and withdrawal of the plunger 54 causes fluid to flowthrough the flow line in a direction determined by the orientation of afirst one way valve 21 and a second one way valve 22.

Referring now to FIG. 30, an embodiment of a pumping device using aplunger 54 and a barrel 52 is shown. In this embodiment, a shape memoryactuator 278 in the form of a wire positioned in a shaft within theplunger 54 is used to impart force on the plunger. The shape memoryactuator 278 extends from a plunger cap 272 through a shaft in a plunger54 and through a channel 58 to a supporting base 299. O-rings 281 and282 seal the plunger 54, barrel 52, and channel 58. Application ofelectrical current to a first lead 258 and a second lead 257 causesheating of the shape memory actuator 278 which results in contraction ofthe shape memory actuator 278. Contraction of the shape memory actuator278 causes a downward force sufficient to overcome the upward bias of areturn spring 276 to be exerted on the plunger cap 272, thereby drivingthe plunger 54 into the lumen 290 of the barrel 52. Expansion of theshape memory actuator 278 allows the return spring 276 to return theplunger 54 to a withdrawn position. The insertion and withdrawal ofplunger 54 causes fluid to flow through the flow line in a directiondetermined by the orientation of a first one way valve 21 and a secondone way valve 22.

An alternate embodiment of the pumping mechanism is shown in FIG. 31.The pumping actuation member is an assembly 101 that combines thefunctions of a reservoir and pumping mechanism. Under the command of acontroller 501, a motor 25 drives a plunger 102 to create pressure in areservoir 104, thereby forcing fluid through a first one way valve 106.Fluid then enters the resilient dispensing chamber 122 of a volumesensing assembly 120 with a sensor 550, and to an exit assembly 17. Anoptional second one way valve 107 may be included. Feedback controlbetween the sensor 550 and the motor 25 via the controller 501 assuresthe desired flow of fluid to the patient. The first one way valve 106serves to prevent reverse flow of fluid due to the resilient force ofthe dispensing chamber 122 of the volume sensing assembly 120 when thechamber is filled and extended. The second one way valve 107 serves toprevent reverse flow of fluid from the exit assembly 17 or patient 12into the dispensing chamber 122. In this embodiment, the sensor 550 canimmediately detect the volume in the dispensing chamber 122.

FIGS. 32-34 schematically show sectional views of a combined valvingpump 2200. FIG. 32 shows the valving pump 2200 with a collection chamber2345 and a pumping chamber 2350 in a resting position, prior toactuation; FIG. 33 shows the valving pump 2200 in an actuating stateduring a compression stoke; and FIG. 34 shows the pump in an actuatedstate at the end of a compression stroke. A pump inlet 2310 is in fluidcommunication with an upstream fluid source, such as a reservoir, andconnects to a first end of a channel 2360. The channel 2360 connects ata second end to the collection chamber 2345, which is in fluidcommunication with a diaphragm aperture 2390 disposed in a resilientpumping diaphragm 2340. The collection chamber 2345 is bounded on afirst side by the resilient pumping diaphragm 2340 and on a second sideby a resilient pumping membrane 2330. The pumping membrane 2330 may bemade from, among other things, latex or silicone rubber. The downstreamside of the diaphragm aperture 2390 opens into the pumping chamber 2350.During priming of the pump and between actuation cycles, fluid travelsfrom a fluid source such as a reservoir, through the pump inlet 2310,the channel 2360, the collection chamber 2345, and the diaphragmaperture 2390, and then arrives in the pumping chamber 2350. A one wayvalve 22 prevents fluid from leaving the pumping chamber 2350 via a pumpoutlet 2370 until and unless ample fluid pressure is exerted against theone way valve 22 such that the one way valve 22 is open. In FIG. 32 apumping actuation member 2320 is shown in a resting position, and theresilient pumping membrane 2330 is shown in a relaxed configuration ofminimal surface area, thereby maximizing the volume of the collectionchamber 2345. Although in this embodiment, the pumping actuation memberis shown as a ball, in other embodiments, the pumping actuation membercan be anything capable of actuation and applying ample force againstthe resilient pumping membrane 2330 in order to actuate the pumpingmechanism.

As can be seen from FIG. 33, when the pumping actuation member 2320 isactuated during a compression stroke, the pumping actuation member 2320begins to travel toward the diaphragm aperture 2390 of the resilientpumping diaphragm 2340 and distends the resilient pumping membrane 2330,causing retrograde flow of fluid that has collected in the collectionchamber 2345. Later in the force application stroke, as shown in FIG.34, the pumping actuation member 2320 will sealingly lodge the resilientpumping membrane 2330 against the diaphragm aperture 2390. To aid insealing, the pumping actuation member 2320 may have a shape that iscomplementary to the shape of the diaphragm aperture 2390. For example,the pumping actuation member 2320 may be spherical or conical and thediaphragm aperture 2390 may be a cylindrical through-hole. At this stageof the force application stroke, retrograde flow from the pumpingchamber 2350 will be inhibited. Continued travel of the pumpingactuation member 2320 will deform the resilient pumping diaphragm 2340and increase the pressure in the pumping chamber 2350, while continuingto seal the diaphragm aperture 2390 against retrograde flow from thepumping chamber 2350. When the pressure within the pumping chamber 2350provides ample fluid pressure against the one way valve one way valve22, fluid will flow from the pumping chamber 2350 through the pumpoutlet 2370. During the return stroke, the pumping actuation member2320, resilient pumping membrane 2330 and resilient pumping diaphragm2340 return to the relaxed positions shown in FIG. 32. During the returnstroke, the internal pressure of pumping chamber 2350 and collectionchamber 2345 will drop, which should encourage refilling of the valvingpump 2200 by inducing flow of fluid from the fluid source through thepump inlet 2310 and channel 2360.

Referring now to FIG. 35, a schematic sectional view of one embodimentof a resilient pumping diaphragm 2340 is shown. A diaphragm body 2515may be constructed of a resilient material such as silicone rubber. Adiaphragm spring 2510 may also be included to impart resiliency to aflexible, or already resilient, body 2515. The diaphragm spring 2510 maybe embedded within the resilient pumping diaphragm 2340 or disposedadjacent to the resilient pumping diaphragm 2340. An example of oneembodiment of a diaphragm spring 2510 can be seen in FIG. 36. Acombination of a diaphragm body 2515 that includes a compliant material,and a diaphragm spring 2510 that includes a resilient material may beused; the result is a pumping diaphragm 2340 that will exhibit a highdegree of sealing when contacted with the resilient pumping membrane2330 deformed by a pumping actuation member (not shown, see FIGS. 32-34)and also have a high degree of resiliency. A valve seat 2517 may bepositioned around the diaphragm aperture 2390. The valve seat 2517 mayfunction as a receptacle for the deformed portion of the resilientpumping membrane 2330 The force application member 2320 may deform thepumping membrane 2330, causing the membrane 2330 to deform and sealinglycontact the valve seat 2517. If sufficient force is applied, the valveseat may be resiliently deformed to ensure a thorough seal againstretrograde flow of fluid. The ratio of the section height to the sectionwidth of the valve seat 2517 can generally be selected differently andmatched to the circumstances of the flow.

Now referring to FIG. 36, an example of a diaphragm spring 2510 for usein the pumping diaphragm 2340 of FIG. 35 is shown. An outer annulus 2520and an inner annulus 2540 are connected by at least three resilient arms2530. The center of the inner annulus 2540 has a spring aperture 2550,which may be aligned with the diaphragm aperture 2390 of the pumpingdiaphragm 2340 as shown in FIG. 35.

Referring now to FIG. 37, a schematic is shown representing a sectionalview of the valving pump 2200 previously shown in FIGS. 32-34 incombination with a force application assembly which includes a pumpingactuation member 2320, an actuator, and a lever 273. When energized byan actuator, such as a shape memory actuator 278, the lever 273 pivotsaround a fulcrum 274 to initiate a compression stroke. A hammer 2630protrudes from the lever 273. During the compression stroke, the hammer2630 contacts a rounded pumping actuation member 2320, causing thepumping actuation member to travel within a void in a support structure2660, and pushing the pumping actuation member 2320 against a resilientpumping membrane 2330 until the pumping actuation member 2320 is heldsealingly against a diaphragm aperture 2390 located in the resilientpumping diaphragm 2340. As the lever 273 continues travel, the pumpingactuation member 2320 causes deformation of a pumping diaphragm 2340.When enough fluid pressure is exerted onto the one way valve 22, the oneway valve 22 opens. This allows the fluid to flow from a pumping chamber2350 through a pump outlet 2370. Upon cooling of the shape memoryactuator 278, the resiliency of the pumping diaphragm 2340 and theresilient pumping membrane 2330 will cause return of the lever 273 to astarting position determined by a lever stop 2650 and lever catch 2640.Alternately, a return spring (not shown) may be used to return the lever273 to the starting position. Although shown as a sphere, the forceapplication member 2320 may alternately be a piston, a protrusion of thelever 273 or other suitable form.

FIG. 38 schematically shows a sectional view of an embodiment of avalving pump using a resilient cylindrical flexure 2670. In oneembodiment, the resilient cylindrical flexure is made from rubber, butin other embodiments, it can be made from any resilient material. Thecylindrical flexure 2670 has a central passageway 2675, and a pluralityof resilient radial fins 2672 that are sealingly arranged against ahousing 2673. Fluid entering through a pump inlet 2310 passes through achannel 2360 and collects in regions upstream of a one way valve 22: acollection chamber 2345, the central passageway 2675 of the cylindricalflexure 2670, and a pumping chamber 2350. The pumping chamber is coupledin fluid communication with the collection chamber 2345 through thecentral passageway 2675. During the pumping mechanism's compressionstroke, a pumping actuation member 2320 applies force to, and deforms, aresilient pumping membrane 2330 until the resilient pumping membrane2330 is sealingly held against a valve seat 2680 of the cylindricalflexure 2670; retrograde flow to the pump inlet 2310 from the collectionchamber 2345 is thereby blocked. Continued travel of the pumpingactuation member 2320 causes deformation of the cylindrical flexure2670; the pressure within the pumping chamber 2350 increases until suchtime that it is ample to open the one way valve 22. Fluid can then flowsthrough a pump outlet 2370.

The pumping actuation member 2320 is shown as a ball shape in FIG. 38.However in other embodiments, the pumping actuation member 2320 can beany shape that can function as described above.

Referring now to FIG. 39, an alternate embodiment of the cylindricalflexure 2670 (shown in FIG. 38) employing a resilient portion 2680 and arigid cylindrical support 2690 is shown. Like the cylindrical flexure2680 of FIG. 38, the resilient portion of the cylindrical flexure 2670includes a valve seat 2680 which seals the central passageway 2675 uponapplication of force by a pumping actuation member 2320. Thus, theresilient portion 2680 of the cylindrical flexure 2670 deforms totransmit pressure to the pumping chamber 2350.

FIGS. 40-44 schematically show sectional views of an alternateembodiment of a valving pump in various states of actuation. The valvingpumps 2200 of FIGS. 40-44 have a resilient diaphragm spring 6100 and aresilient sealing membrane 6120 which together serve a function that issimilar to that of the resilient pumping diaphragm 2340 of the valvingpump 2200 shown in FIGS. 32-34. FIG. 40 shows the valving pump 2200 in aresting state. In the resting state, fluid may flow from the inlet 2360,into an upper portion 2346 of the collection chamber 2345, through anaperture 6110 in the diaphragm spring 6100 and into a lower portion 2347of the collection chamber 2345. Fluid then may proceed through one ormore openings 6130 in a sealing membrane 6120 and into the pumpingchamber 2350. Under low-pressure conditions, further fluid flow ishindered by a one way valve 22. The spring diaphragm 6100 and sealingmembrane 6120 may both be constructed from resilient, biocompatiblematerials. The spring diaphragm 6100 may have a greater resiliency thanthe sealing membrane 6120. For example, the spring diaphragm 6100 may bea circular piece of flexible bio-inert plastic and the sealing membrane6120 may be a sheet of silicone or fluorosilicone elastomer.

FIGS. 41 and 42 show the valving pump 2200 in two intermediate,partially actuated states. The pumping actuation member 2320 deforms thepumping membrane 2330 and forces it through the collection chamber 2345and against the spring diaphragm 6100, which, in turn, is deformed andforced against the sealing membrane 6120. At this point in thecompression stroke, retrograde flow through either the aperture 6110 ofthe spring diaphragm 6100, or through openings 6130 in the sealingmembrane 6120, or both, are suppressed. Offset placement of the sealingmembrane openings 6130 relative to the spring aperture 6100 allows aseal to be created between the spring diaphragm 6100 and the sealingmembrane 6120. In some embodiments this seal may be supplemented with aredundant seal between the fill chamber resilient pumping membrane 2330and the spring diaphragm 6100 (the embodiments of FIGS. 43-44, forexample, lack this redundant seal). A circumferential ridge (not shown)around the spring diaphragm aperture 6110 may act as a valve seat toenhance the seal.

Referring now to FIG. 42, continued travel of the pumping actuationmember 2320 causes further deformation of the pumping membrane 2330,spring diaphragm 6100, and sealing membrane 6120. As a result, fluid inthe pumping chamber 2350 is compressed until the fluid pressure forcesthe one way valve 22 open; further compression causes fluid egressthrough the outlet 2370.

An alternate embodiment of the valving pump 2200 of FIGS. 40-42 is shownschematically in FIG. 43. In this embodiment, a pumping actuation member2320 traverses the resilient pumping membrane 2330. The pumping membrane2330 is sealingly attached to the circumference of the pumping actuationmember 2320 at a midpoint along the length of the pumping actuationmember 2320. When actuated, the diaphragm spring aperture 6110 is sealedagainst backflow by the sealing membrane 6120 alone; the resilientpumping membrane 2330 will not contact the aperture 6110. An alternateembodiment of the device shown in FIG. 40 is shown in FIG. 44.

Referring now to FIG. 45, a sectional view of an alternate embodiment ofa combined valving pump 2200 is shown. A shape memory actuator 278actuates a compression stroke which causes a resilient pump blade 2710to lever about a fulcrum 274, causing the resilient pumping membrane2330 to be deformed. The resilient pump blade 2710 and resilient pumpingmembrane 2330 apply pressure to fluid in a graded pumping chamber 2720having a shallow region 2730 and a deeper region 2740. Early in thecompression stroke, the pump blade 2710 induces the resilient pumpingmembrane 2330 to obstruct a channel 2360 that connects a pump inlet 2310to the graded pumping chamber 2720. As the compression stroke continues,force is applied to the fluid in the graded pumping chamber 2720 untilthe fluid pressure in the graded pumping chamber 2720 is great enough toopen a one way valve 22. Fluid then exits a pump outlet 2370. The pumpblade 2710 may be constructed entirely or partly from a resilientmaterial such as rubber. In some embodiments, the resilient materialincludes a non-resilient spline. Alternately, in some embodiments, theresiliency is imparted through a resilient region 2750, thus, theresilient region 2750 is the only resilient part of the pump blade 2710in these embodiments. In these embodiments, the resilient region 2750contacts the bottom of the graded pumping chamber 2720. The resiliencyof pump blade 2710 allows the compression stroke to continue after thepumping blade 2710 contacts the base 2780 of the shallow region 2730. Areturn spring (not shown) returns the pump blade 2710 to a startingposition during the return stroke.

Referring now to FIG. 46, a sectional view of an alternate embodiment ofa pumping mechanism is shown. This embodiment includes a resilient pumpblade 2710. The resilient pump blade 2710 includes a resilient region2830 which provides resiliency to the pump blade 2710. The resilientregion 2830 joins a pumping actuation member 2820 to a pump blade 2810.When used with a valving pump (not shown) the resilient pump blade 2710of FIG. 42 will occlude the inlet channel (not shown, shown in FIG. 45as 2360) and then bend at the flexible region 2830 to allow the forceapplication member 2820 to apply further pressure to the fluid in thegraded pumping chamber (not shown, shown in FIG. 45 as 2720). The forceapplication member 2820 may be constructed entirely of a resilientmaterial such as rubber. However, in alternate embodiments, only aregion that contacts the bottom of the pumping chamber (not shown) ismade from resilient material. The resilient pump blade 2710 will returnto its relaxed conformation during the return stroke.

Referring now to FIG. 47, a sectional view of another embodiment ofpumping mechanism is shown. The pumping mechanism is shown where thelever is at the intermediate stage of actuation with the inlet valve2941 closed. The pumping mechanism includes a fluid line 2930, amoveable member 2330, which is a membrane in this embodiment, an inletvalve 2941 poppet 2940, a pumping actuation member 2942, a pumpingchamber 2350, and an exit valve 22. The inlet valve 2941 and the pumpingactuation member 2942 are each actuated by the shape memory actuator 278which is surrounded by return spring 276 and connected to a lever 273.The lever 273 actuates both the inlet valve 2941 and the pumpingactuation member 2942. The lever 273 includes an elongate and springmember 2910 that is attached to the lever 273 hinged to fulcrum 274 andterminated in a valve actuation hammer 2946. The spring member 2910 maybe curved. The spring member 2910 biases the position of the valveactuation hammer 2946 away from the lever 273 and toward the inlet valve2941. The lever 273 has a pump actuation hammer 2948, which is notattached to the spring member 2910, and is positioned adjacent to thepumping actuation member 2942.

Electric current causes the shape memory actuator 278 to contract andthe lever 273 pivots about the fulcrum 274. The pivoting places thevalve actuated hammer 2946 in position to force the inlet valve 2941closed. As the shape memory actuator 278 continues to contract, thelever 273 continues pivoting and the pump actuation hammer 2948 forcesthe pump actuation member 2942 against the pumping chamber 2350, evenwhile further compressing the elongate spring member 2910. Uponachieving sufficient pressure, the fluid pressure opens the exit valve22, and fluid exits through the valve.

During the relaxation stroke, the return spring 276 unloads and returnsthe lever 273 to the starting position, releasing the pumping actuationmember 2942. The inlet valve 2941 opens. The resiliency of the pumpingchamber 2350 causes the pumping chamber 2350 to refill.

Referring now to FIGS. 48 and 49 schematically show a cross section ofan embodiment in which a pumping mechanism employs a bell crank 7200 andcombines a valving pump 2200 with a flow biasing valve. The bell crack7200 converts force produced by the linear shape memory actuator 278into a transverse pumping force. FIG. 48 shows the mechanism in aresting or refilling mode and FIG. 49 shows the mechanism in an actuatedstate. Contraction of the actuator 278 causes the bell crank 7200 torotate around a shaft 7210 and press upon the force application member2320, which drives a resilient membrane 7220 to seal against theresilient pumping diaphragm 2340 and urge fluid from the pumping chamber2350 toward the dispensing chamber 122. The return spring 276 cooperateswith a return spring support 7221 to release the pumping force, causingthe pumping chamber 2350 to expand and draw fluid from the reservoir 20.Still referring to FIGS. 48 and 49, the flow biasing valve 4000 is alsoshown, having a valve spring 4010, a poppet or plunger 4020.

In some of the embodiments of the pumping mechanism described above, oneor more aspects of the following valving operation description isrelevant. Referring now to FIG. 50, an example of a flow biasing valve4000 is shown, closed. A valve spring 4010 exerts force on a poppet 4020to sealingly press a valve membrane 4060 against a valve seat 4070surrounding a terminal aperture of a valve outlet 4040. The valve seat4070 may include a circumferentially raised portion to improve sealing.As explained below with references to FIGS. 54-55, back pressure createdby the action of a resilient dispensing assembly should be insufficientto cause retrograde flow through the flow biasing valve 4000. As shownin FIG. 51, when the pumping assembly is actuated, sufficient pressureshould be generated to unseat the membrane 4060 and the poppet 4020 fromthe valve seat 4070 thereby allowing fluid to flow from the valve inlet4030, through an inlet chamber 4050 and to the valve outlet 4040. FIGS.52-53 shows an alternate valve that has a valve seat 4070 without acircumferentially raised portion.

Referring now to FIGS. 54 and 55, illustrations of how an exemplary flowbiasing valve discriminates between forward and retrograde flow areshown. FIG. 54 schematically represents the valve in a closed position.Back pressure in the outlet 4040 applies force to a relatively smallarea of the flexible valve membrane 4060 adjacent to the valve seat 4070and is thus unable to dislodge the poppet 4020. Referring now to FIG.55, this FIG. schematically represents the valve during the actuation ofa pumping actuation member. The pressure of the pumped fluid appliesforce over an area of the membrane 4060 that is larger than the areaadjacent to the valve seat. As a result, inlet pressure has a largermechanical advantage for unseating the poppet 4020 and forward flowshould ensue in response to the action of the pumping actuation member.Thus, the critical pressure needed to displace the poppet 4020 is lowerin the inlet than in the outlet. Accordingly, the spring biasing forceand the size of the force application areas associated with both thefluid inlets and fluid exits may be chosen so that flow is substantiallyin the forward direction.

Referring now to FIG. 56, a sectional view of an adjustable flow biasingvalve 4130 which operates on a principal similar to the flow biasingvalve in FIG. 50, but allows adjustment of the pressure necessary toopen the valve, i.e., “cracking pressure” (which, in some embodiments,can be from 0.2 to 20 pounds per square inch or “psi”) is shown. Thecracking pressure is adjusted by turning a spring tensioning screw 4090,which alters the volume of the recess 4080 to compress or decompress thevalve spring 4010 thereby altering the spring 4010 biasing force. Thevalve spring 4010 biases a plunger 4100 against the valve membrane 4060to force it against the valve seat. The plunger 4100 serves a forceapplication function similar to the fixed force poppet of the flowbiasing valve (shown as 4020 and 4000 respectively, in FIGS. 50-53).Compressing the valve spring 4010 will increase its bias, therebyincreasing the cracking pressure. Conversely, decompressing the spring4010 will decrease its bias and the associated cracking pressure. Thevalve spring 4010 is positioned coaxially around the shaft of a plunger4100 and exerts its biasing force on the plunger 4100. In someembodiments, the shaft of the plunger 4100 may be shorter than both thelength of the valve spring 4010 and the recess 4080 to allow it to befreely displaced in response to increased fluid pressure in the fluidinlet 4030. The plunger 4100 may be any size necessary to function asdesired. As in the embodiment of FIGS. 50-53, the wetted parts mayreside in a disposable portion 2610 and the force application components(e.g., the plunger and spring) may reside in the reusable portion 2620.The principal of operation is also similar; a larger mechanicaladvantage in the fluid inlet 4030 relative the outlet 4040 favorsforward flow versus retrograde flow. Alternately, the plunger 4100 maybe replaced by the poppet (shown as 4020 in FIGS. 50-55). In someembodiments, it may be desirable to eliminate the raised valve seat; inthese embodiments, the plunger may be ball shaped or another shapecapable of concentrating the force.

The flow biasing valve 4000 substantially reduces or prevents retrogradeflow from the dispensing chamber 122 into the pumping chamber 2350. Asin FIGS. 50-56, a valve spring 4010 biases a poppet or plunger 4040 topress the membrane 7220 against a valve seat 4070 in a way that providesmechanical advantage to forward flow through the line 310. By servingthe function of the pumping membrane 2330 and the valve membrane,membrane 7220 allows the line 310, pumping chamber 2350 and pumpingdiaphragm 2340 to reside in one component (e.g., the disposable portion2610) and the remainder of the pumping mechanism in a second, removablecomponent (e.g., the reusable portion 2620). By placing the more durableand expensive components in the reusable portion 2620, economy andconvenience may be realized.

The pumping mechanism described in the various embodiments above can beused in various devices to pump fluid. As an exemplary embodiment, thepumping mechanism described in FIGS. 59A-59E, FIGS. 60A-60D and FIGS.60A-60C will be described as integrated into a fluid pumping device.

Referring FIGS. 57 and 58, alternate ways are shown for the fluidschematic. These are two schematics where the reservoir 20 and pumpingassembly 16 are coupled to the dispensing assembly 120. In theembodiment shown in FIG. 57, the reservoir and pumping assembly arecoupled in series to the dispensing assembly 120. In the embodimentshown in FIG. 58, a shunt line 150 is coupled from the output of thepumping assembly 16 back to the reservoir 20. Since much of the fluidoutput of the pumping assembly 16 is returned to the reservoir 20 viathe shunt line 150, the pumping assembly 16 can accommodate varieties ofpumping mechanisms 16 that may not function as desired in the embodimentshown in FIG. 57. Thus, in some embodiments, where a large volumepumping mechanism is employed, the shunt line 150 can impart smallvolume functionality to a large volume pumping mechanism. One way valves21 and 22 are oriented in the same direction and included to preventunwanted backflow.

Referring now to FIG. 59A, a fluid schematic of one embodiment of afluid pumping device is shown. In this embodiment, fluid is located in areservoir 20 connected to a fluid line 310. Fluid line 310 is incommunication with pumping mechanism 16, separated by a membrane 2356.The fluid is pumped through a flow restrictor 340 to an infusion deviceor cannula 5010 for delivery to a patient. It should be understood thatthe infusion device or cannula 5010 is not part of the device as such,but is attached to a patient for delivery of the fluid. Systemembodiments are described in more detail below and these include aninfusion device or cannula 5010.

Referring now to FIG. 59B, an alternate embodiment of the schematicshown in FIG. 59A is shown. In the embodiment shown in FIG. 59A, thefluid is pumped through a flow restrictor 340 then through a cannula5010. However, in FIG. 59B, the fluid is not pumped through a flowrestrictor; rather, the fluid is pumped, having the same impedance,through the cannula 5010.

In both FIGS. 59A and 59B, the volume of fluid pumped to the patient, inone embodiment, is calculated roughly by pump strokes. The length of thestroke will provide for a rough estimate of the volume pumped to thepatient.

Referring now to FIG. 59C, a fluid schematic of one embodiment of afluid pumping device is shown. In this embodiment, fluid is located in areservoir 20 connected to a fluid line 310 by a septum 6270. Fluid line310 is in communication with pumping mechanism 16, separated by amembrane 2356. The fluid is pumped to a variable volume delivery chamber122 and then through a flow restrictor 340 to a cannula 5010 fordelivery to a patient.

The volume of fluid delivered is determined using the dispensingassembly 120 which includes an acoustic volume sensing (AVS) assembly,as described above, a variable volume delivery chamber 122, and adispensing spring 130. Similarly to the pumping mechanism, a membrane2356 forms the variable volume dispensing chamber 122. The membrane ismade of the same material (or, in some embodiments, different material)from the membrane 2356 in the pumping mechanism 16 (described in detailabove). The AVS assembly is described in greater detail above.

Referring now to FIG. 59D, an alternate embodiment to the embodimentshown in FIG. 59C, in this embodiment, there is no flow restrictorbetween the variable volume delivery chamber 122 and the cannula 5010.Referring now to FIG. 59E, an alternate embodiment to the embodimentshown in FIG. 59C is shown, with an alternate pumping mechanism 16.

Referring now to FIGS. 59A-59E, the reservoir 20 can be any source of afluid, including but not limited to a syringe, a collapsible reservoirbag, a glass bottle, a glass vile or any other container capable ofsafely holding the fluid being delivered. The septum 6270 is theconnection point between the fluid line 310 and the reservoir 20.Various embodiments of the septum 6270 and the reservoir 20 aredescribed in more detail below.

The fluid delivery device embodiment shown in FIGS. 59A-59E can be usedfor the delivery of any type of fluid. Additionally, the embodiments canbe used as one, two or three separate mating parts. Referring now toFIGS. 60A-60D, the same embodiments described with respect to FIGS.59A-59D are shown as separated into mating parts. Part X includes themovable parts while part Y includes the fluid line 310 and the membrane2356. In some embodiments of this design, part Y is a disposable portionwhile part X is a non-disposable portion. Part X does not come intocontact directly with the fluid, part Y is the only part having wettedareas. In the above embodiments, the reservoir 20 can any size and iseither integrated into the disposable or a separate disposable part. Ineither embodiment, the reservoir 20 can be refillable. In embodimentswhere the reservoir 20 is integrated into the disposable part Y, thereservoir 20 can either be manufactured filled with fluid, or, a patientor user fills the reservoir 20 using a syringe through the septum 6270.In embodiments where the reservoir 20 is a separate mating part, thereservoir 20 can either be manufactured filled with fluid, or, a patientor user fills the reservoir 20 using a syringe (not shown) through theseptum 6270 as part of a reservoir loading device (not shown, describedin more detail below) or manually using a syringe through the septum6270. Further detail regarding the process of filling a reservoir 20 isdescribed below.

Although various embodiments have been described with respect to FIGS.59A-59E and FIGS. 60A-60D, the pumping mechanism can be any pumpingmechanism described as embodiments herein or alternate embodimentshaving similar function and characteristics. For example, referring nowto FIG. 61A, a similar embodiment as that shown in FIG. 59A is shownhaving a representative block that includes pumping mechanism 16. Thisis to show that any pumping mechanism 16 described herein or functioningsimilarly can be used in the fluid pumping device. Likewise, FIG. 61Band FIG. 61C are representations of systems encompassing the embodimentsFIG. 59B and FIG. 59C respectively.

The schematics of a fluid pumping device described above can beimplemented in a device usable by a patient. There are a number ofembodiments. The device can be a stand-alone device or be integratedinto another device. The device can be any size or shape. The device canbe either portable or non-portable. The term “portable” means a patientcan, transport the device either in a pocket area, strapped to the body,or otherwise. The term “non-portable” means that the device is in ahealthcare institution or in the home, but the patient does not carrythe device almost everywhere they move. The remainder of thisdescription will focus on portable devices as the exemplary embodiment.

With respect to portable devices, the device can be worn by a patient orcarried by a patient. In the embodiments where the device is worn by apatient, this is referred to as a “patch pump” for purposes of thisdescription. Where the device is carried by a patient, this is referredto as a “portable pump” for purposes of this description.

The following description is applicable to various embodiments foreither the patch pump embodiments or the portable pump embodiments. Invarious embodiments, the device includes a housing, a pumping mechanism,a fluid line, a moveable member, a reservoir, a power source and amicroprocessor. In various embodiments, a dispensing assembly, forexample a volume sensing device, which in some embodiments includes anAVS assembly, are included in the device. Also, an embodiment can alsoinclude a fluid restrictor, although it is not depicted in the followingfigures, as the fluid line is shown as homogeneous to simplify theillustration. For purposes of this description, where a dispensingassembly is included, the exemplary embodiment will include an AVSassembly. Although an AVS assembly is a preferred embodiment, in otherembodiments, other types of volume sensing device can be used. In someembodiments, however, no volume sensing device is used, but rather,either the reservoir itself will determine the volume of fluiddelivered, the pump stroke is used to roughly determine the amount ofvolume delivered. It should be understood that the schematic devicesshown herein are meant to illustrate some of the variations in thedevice. The embodiments represented by these schematics can each alsoinclude a sensor housing, a vibration motor, an antenna, a radio, orother components that are described with respect to FIGS. 70-70D. Thus,these depictions are not meant to limit the components but rather toillustrate how various components could interrelate in a device.

Referring now to FIG. 62A, schematics of a stand alone device 10 areshown. The housing 10 can be any shape or size and accommodates theintended use. For example, where the device is used as a patch, thedevice will be compact enough to be worn as such. Where the device isused as a portable pump, the device will be compact enough to be usedaccordingly. In some embodiments, the housing is made from plastic, andin some embodiments, the plastic is any injection moldedfluid-compatible plastic, for example, polycarbonate. In otherembodiments, the housing is made from a combination of aluminum ortitanium and plastic or any other material, in some embodiments thematerials are light and durable. Additional materials may include, butare not limited to, rubber, steel, titanium, and alloys of the same. Asshown in FIG. 62A, the device 10 can be any size or shape desired.

FIGS. 62A-69B are schematics showing representative embodiments. Theexact design is dependant on many factors, including, but not limitedto, size of the device, power restrictions and intended use. Thus, FIGS.62A-69B are intended to describe the various features of a device andthe possible combinations, however, actual devices can be readilydesigned and implemented by one or ordinary skill in the art. Asexamples, embodiments of devices are described and shown below. However,these are not intended to be limiting, but rather, are intended to beexamples.

Referring now to FIG. 62B, with respect to the patch device, in someembodiments, the housing 10 includes an insertion area viewing window342. This allows for the area on a patient where the infusion device orcannula (not shown) is inserted to be viewed. Shown here is the cannulahousing 5030 area of the device 10. The viewing window 342 is made fromany material capable of being transparent, including, but not limitedto, plastic. Although the viewing window 342 is shown to be in oneparticular location on one particular shaped device, a viewing window342 can be integrated in any location desired in any housing embodiment.

Referring now to FIG. 63A, a device 10 is shown. A reservoir 20 is shownconnected to a fluid line 310, which is then connected to a pumpingmechanism 16. A dispensing assembly 120 is shown connected to the fluidline 310. The pumping mechanism 16 and dispensing assembly 120 areseparated from the fluid line 310 by a membrane 2356. The cannulahousing 5030 is downstream from the volume measuring device. Shapememory actuators 278 are shown connected to the pumping mechanism 16. Amicroprocessor on a printed circuit board 13 as well as a power sourceor battery 15 are included. A flow impedance as described above can alsobe implemented between the dispensing assembly 120 and the cannulahousing 5030.

Referring now to FIG. 63B, a similar device 10 as shown in FIG. 63A isshown, except in this embodiment, a dispensing assembly is not included.In this embodiment, the volume of fluid delivered will depend on eitherthe pump strokes (number and length), the reservoir 20 (volume andtime), both, or any other method described previously with respect tomonitoring the volume of fluid delivered.

Referring now to FIG. 63C, a similar device 10 as shown in FIG. 63B isshown, except the device 10 includes a dispensing chamber 122 and sensorhousing 5022.

Referring now to FIG. 64A, one embodiment of the patch pump device 10 isshown. This embodiment is based on the embodiment of the device 10 shownin FIG. 63A. In this embodiment, the patch pump device 10 is dividedinto two sections: a top X and a base Y. The top X contains the pumpingmechanism 16, a dispensing assembly 120 (which is optional, but is shownas an exemplary embodiment), the power supply 15, and the microprocessorand printed circuit board 13. These are the non-wetted elements, i.e.,they do not come into direct contact with the fluid. The base Y containsthe fluid line 310 and the membrane 2356. Where the reservoir 20 isbuilt into the device, the reservoir is also contained on the base Y.However, in embodiments where the reservoir 20 is a separate matingpart, the reservoir 20 is connected to the fluid line when fullyassembled (see FIGS. 66A-66D and description referring thereto),however, is not built into the device.

The patch pump device also includes a cannula housing 5030. This is thearea the cannula line 5031 is located. Part of the fluid line 310, thecannula line 5031 allows a cannula (or other infusion device) to receivethe fluid and deliver the fluid to a patient (not shown).

Referring now to FIG. 65A, in some embodiments, the cannula 5010 isinserted through the housing 5030 directly into the patient. The cannula5010 is connected to a septum (not shown) connecting the cannula line5031 to the cannula 5010. Referring now to FIG. 65B, in otherembodiments, an insertion set, (including the cannula and tubing, notshown in FIG. 65B, but shown in FIG. 64B as items 5033 and 5010) isused; thus, the tubing 5033 of the insertion set will connect to thecannula line 5030 on one end and will connect to the cannula (not shown)on the opposite end of the tubing.

Referring again to FIG. 64A, in use, the reservoir 20, having fluidcontained inside (which, as described above, is either molded into thebase Y or is separate and attached to the base Y) is connected to thefluid line 310. The microprocessor on the printed circuit board 13 sendsa signal to activate the pumping mechanism 16 and a stroke is initiatedthrough electrical current being applied to the shape memory actuators278. The fluid flows from the reservoir 20, in the fluid line 310 to thedispensing assembly 120, or AVS assembly. There, the exact volume offluid inside the AVS chamber is determined and the fluid is forced outof the AVS chamber, to the cannula line 5031 and the cannula housing5030.

Referring now to FIG. 64B, the device shown in FIG. 64A is shownconnected to an insertion set, tubing 5033 and cannula 5010. In FIG.64C, the base Y of the device is shown using an adhesive patch or pad3100 to the body of a patient 12. It should be noted that in thisembodiment, the element 3100 can be either a pad or patch. However, asdescribed in more detail below, item 3100 is called a patch, and item3220 is called a pad. For simplicity purposes only, item 3100 is used;however, in some embodiments, a pad is used, thus item 3220 would beappropriate in those circumstances.

The cannula 5010, which is inserted through the cannula housing 5030 sothat it mates by way of the cannula septum 5060 to the cannula line5031, is inserted into a patient 12. However, as shown and describedabove with respect to FIG. 2B, the base Y can be fluidly attached to apatient through an insertion set, which includes a tubing 5033 and acannula 5010. In both FIGS. 64B and 64C, the base Y can be adhered to apatient either before or after insertion of the cannula 5010. Referringagain to FIG. 2C, the cannula 5010, once inserted into to the patient12, will receive fluid from the device directly without an infusion settubing (shown in FIG. 64B). The base Y is adhered to the patient 12 withan adhesive patch 3100 either before or after insertion of the cannula5010. Referring now to FIG. 64D, the top X of the device 10 is thenattached to the base Y of the device 10 after the cannula 5010 has beeninserted into the patient 12.

As described below, the adhesive patch can have many embodiments and insome cases, the patch is placed on top of the device. Thus, the patchshown in these embodiments is only one embodiment. As described above, apad, if used, would be placed in the same location as the patch in FIGS.64A-64D.

Referring now to FIGS. 66A-66D, in this embodiment, the reservoir 20 isshown as a separate part. As shown in FIG. 66A, the base Y includes areservoir cavity 2645 with a septum needle 6272. Shown in FIG. 66B, thereservoir 20 is first placed in a top reservoir cavity 2640. At thispoint, the reservoir 20 is not attached to the device. Now, referring toFIG. 66C, when the top X is placed over the base Y, the reservoir 20 issandwiched into the base reservoir cavity 2645. Shown in FIG. 66D, theforce created by the attachment of the top to the base Y push the septumneedle 6272 into the septum 6270 of the reservoir 20 connecting thereservoir 20 to the fluid line 310 of the base Y.

Referring now to FIGS. 67A-F, alternate embodiments of the embodimentsshown in FIGS. 64A, 64C and 66A-66D are shown. In these alternateembodiments, in addition to a cannula housing 5030, the base Y includesa sensor housing 5022. Referring now to FIGS. 69A-69B, both the sensorhousing 5022 and the cannula housing 5030 include an exit to theunderside of the base Y, shown in FIG. 69A as 5022 and 5030respectively. FIG. 69B depicts the embodiment shown in FIG. 69A with thesharps protruding through the housings. The sensor housing accommodatesa sensor. In some embodiments, the sensor is an analyte sensor. Analytessensed include blood glucose, but in other embodiments, this analytesensor can be any type of analyte sensor desired.

Referring now to FIG. 67B, the base Y is shown on the body of a patient12. The sensor 5020 is shown having been inserted through the base Ysensor housing 5022 and into the patient 12. Referring now to FIG. 67C,in some embodiments, the cannula 5010 and sensor 5020 are insertedthough their respective housing (5030 and 5022) and into the patient 12simultaneously. Referring next to FIG. 67D, the base Y is shown attachedto the patient with both a cannula 5010 and sensor 5020 attached to thepatient 12 through the base Y.

Referring now to FIG. 67E, the base Y is shown attached to a patient 12and the cannula 5010 inserted through the cannula housing 5030. In thisembodiment, the sensor housing 5022 is shown without a sensor. However,a sensor 5020 is shown inserted into the patient 12 in another location.Thus, the sensor 5020 is not required to be inserted through the base Y,but embodiments described below relating to monitoring blood glucose andpumping insulin through a cannula can be implemented in this way.Additionally, other embodiments relating to administering a fluid inresponse or relation to an analyte level can be administered this way.

Referring now to FIG. 67F, the device 10, having both a sensor 5020 anda cannula 5010 through the base Y is shown with the top X placed on.Again, in the embodiments shown in FIGS. 66A-66D, once the top X isplaced onto the base Y, the reservoir 20 is fluidly connected to thefluid line 310.

Referring now to FIG. 68, one embodiment of the portable pump embodimentof the device 10 is shown. In this device 10, an insertion set,including a cannula 5010 and tubing 5033, is necessary to connect thefluid line in the device 10 to the patient 12. Thus, the cannula 5010 isnot connected, in this embodiment, through the portable pump device 10to the patient 12 directly. Additionally, although this embodiment canfunction as described below with respect to an analyte sensor and afluid pump, the sensor 5020 will be located outside the portable pumpdevice 10 similar to the embodiment of the sensor 5020 shown in FIG. 5F.

Referring now to FIGS. 70-70D, both the patch pump and portable pumpembodiments as described additionally contain various components of thedispensing assembly (in applicable embodiments) and for embodimentsincluding the AVS assembly, the various components thereof, including,at least one microphone, a temperature sensor, at least one speaker, avariable volume dispensing chamber, a variable volume chamber, a portand a reference chamber. In some embodiments, the device contains one ormore of the following: a vibrator motor (and, in those embodiments, amotor driver), an antenna, a radio, a skin temperature sensor, a bolusbutton, and in some embodiments, one or more additional buttons. In someembodiments, the antenna is a quarter-wavelength trace antenna. In otherembodiments the antenna may be a half-wavelength or quarter wavelengthtrace, dipole, monopole, or loop antenna. The radio, in someembodiments, is a 2.4 GHz radio, but in other embodiments, the radio isa 400 MHz radio. In still other embodiments, the radio can be anyfrequency radio. Thus, in some embodiments, the device includes a radiostrong enough to communicate to a receiver within a few feet in distancefrom the device. In some embodiments, the device includes a secondradio. In some embodiments, the second radio may be a specificlong-range radio, for example, a 433 or 900 MHz radio or, in someembodiments, any frequency within the ISM band or other bands, Not shownin FIGS. 70-70D, the device, in some embodiments, contains a screenand/or a user interface.

The following description of these components and the variousembodiments thereof are applicable to both device types, and further, tothe various embodiments described with respect to each device type.Referring now to FIG. 67F, for illustration purposes only, both thecannula 5010 and the sensor 5020 have been inserted into the device 10.Also, referring to FIGS. 70-70D, the various components, some of whichwill not necessarily be included in all embodiments, are shown in aschematic representing the electrical connections of those components.FIGS. 70-70D therefore represent the various elements that could beincluded in the device. These can be mixed and matched depending on sizerequirements, power restrictions, usage and preferences, as well asother variables. FIG. 70 shows the relation of FIGS. 70A-70D.

The device contains at least one microprocessor 271. This can be anyspeed microprocessor capable of processing, at a minimum, the variouselectrical connections necessary for the device to function. In someembodiments, the device contains more than one microprocessor, as seenin FIGS. 70A-70B, the device is shown having two microprocessors 271.

The microprocessor 271 (or in some embodiments, microprocessors) isconnected to the main printed circuit board (hereinafter, the “PCB”refers to the term “printed circuit board”) 13. A power source, which insome embodiments is a battery 15, is connected to the main PCB 13. Inone embodiment, the battery 15 is a lithium polymer battery capable ofbeing recharged. In other embodiments, the battery can be a replaceablebattery or a rechargeable battery of any type.

In some embodiments, the device includes a radio 370 connected to themain PCB 13. The radio 370 communicates to a remote controller 3470using the antenna 3580. The communication between the device 10 and theremote controller 3470 is therefore wireless.

In some embodiments, the device contains a vibration motor 3210. Thevibration motor 3210 is connected to a motor driver 3211 on the main PCB13 motor driver 3211.

Some embodiments include a bolus button 3213. The bolus button 3213functions by a user applying force to a button form 3213, which can bemade from rubber or any other suitable material. The force actuates thebolus button actuation, which is attached to a bolus button switch 3214on the main PCB 13. The switch 3214 activates a single bolus which willindicate a particular pre-determined volume of fluid is to be deliveredto the patient. After the user presses the bolus button 3213, in someembodiments, the device 10 will generate an alarm (e.g., activate thevibration motor 3210 and/or send a signal to the remote controller) tosignal to the user that the button 3213 was pressed. The user will thenneed to confirm the bolus should be delivered, for example, bydepressing the button 3213. In still other embodiments, the remotecontroller 3470 queries the user to confirm the bolus should bedelivered.

A similar query/response sequence may be used in various embodiments totest and report on patient responsiveness. For example, the device maybe configured to test patient responsiveness by generating an alarm(e.g., an audible and/or tactile alarm) and awaiting a response from thepatient (e.g., actuation of the button 3213). Such a test may beperformed at various times (e.g., every five minutes) or upon detectionof a condition such as an abnormal analyte level monitored via ananalyte sensor or an abnormal body temperature monitored via atemperature sensor. If the patient does not provide an appropriateresponse within a predetermined amount of time, the reusable portion maysend an alarm to a remote controller or caretaker. Such testing andreporting might be particularly valuable for patients who could becomeunconscious or incapacitated, either from a device malfunction orotherwise.

The NITINOL circuit (referring to the shape memory actuator, which insome embodiments, is a NITINOL strand) 278 on the main PCB 13 provideselectrical current to the NITINOL connectors. As shown in FIG. 67F andFIG. 70A, the device can include two NITINOL connectors 278 (and twoNITINOL strands). However, as described above, in some embodiments, thedevice includes one NITINOL connector (and one NITINOL strand).

In some embodiments, the device includes a temperature sensor 3216 shownon FIG. 70B The temperature sensor 3216 is located on the underside ofthe base Y and senses the temperature of the patient's skin. The skintemperature sensor 3216 is connected to a signal conditioner,represented by 3217. As shown in FIG. 70B, the signal conditioning 3217is represented as one block, however the device includes multiple signalconditioners, as needed, each filtering different the signals.Following, the AVS temperature sensor 132, AVS microphones 133, andanalyte sensor 5020 are all connected to a signal conditioner,represented in one block as 3217.

The AVS speaker 134 is connected to the speaker drive 135 on the mainPCB 13. The AVS speaker 134, in one embodiment, is a hearing aidspeaker. However, in other embodiments, the speaker 134 (a speakercontaining a voice coil, a magnet with an electromagnetic coil) is apiezo speaker (shown in FIG. 50, representing one embodiment of thedevice).

Referring still to FIGS. 70-70D, in some embodiments, the antenna 3580has a dedicated PCB 3581, which is then connected to the main PCB 13.Also, in some embodiments, the AVS microphones 133 each have a dedicatedPCB 1332, 1333, connected to the main PCB 13. The various PCBs may beconnected to the main PCB 13 using conventional methods, for example,flexible circuits or wires.

Referring to FIG. 67F, the device 10 is shown as an exemplary embodimentfor description purposes. However, the layout of the various parts canvary and many of the embodiments are shown below. However, additionalalternate embodiments are not shown but can be determined based on size,power and use.

In accordance with an alternate embodiment, the disposable portion 2610may include the reservoir 20 and optionally, a battery. The reservoir 20may be integral to the disposable portion or otherwise coupled to thedisposable portion. The battery may be the primary or sole power sourcefor the device or may be a backup power source, and may be used toprovide electrical power to electronics on the reusable portion and/orthe disposable portion. Both the reservoir 20 and the battery willtypically require regular replacement, so including both of thesecomponents in the disposable portion 2610 may provide to the user theincreased convenience of simultaneous replacement. Additionally, byreplacing the battery every time the reservoir is changed, the user maybe less likely to allow the battery to run down.

The disposable portion 2610 could additionally or alternatively includea processor that may be used, for example, to continue certain deviceoperations in the event of a failure (e.g., a failure of a maincontroller in the reusable portion), to generate an alarm in the eventof a failure, or to provide status information to the reusable portion.With regard to status information, the processor could keep track of theoperation history and various characteristics of the disposable and holdstatus information for access by the user, the fluid delivery device 10,and/or the user interface 14 including during installation of thedisposable portion 2610. For instance, the processor can store statusrelated to shelf life, maximum exposure or operation temperature,manufacturer, safe dispensing limits for the therapeutic, etc. If any ofthese status indicators is determined by the device to be unacceptable,the device can refuse to power the pumping assembly and dispensingassembly and indicate to the user that the disposable is not usable. Theprocessor may be powered by a battery in the reusable portion or thedisposable portion.

More generally, the device may be configured to obtain statusinformation from any of the disposables (including, for example, thedisposable portion 2610 and any disposable component used therewith,such as the fluid reservoir, battery, or sharps cartridge or individualsharps component), for example, from a processor disposed in disposableportion, via bar code reader, or via RFID technology. If the devicedetects a problem with the disposables (e.g., invalid model number foruse with the reusable portion or an expiration date of the fluid haspassed), then the device may take remedial action, such as, for example,preventing or terminating operation of the device and generating anappropriate alarm.

Additional components may be included in some embodiments. For example,redundant failure detection and announcement mechanisms can be employed.The device may employ an audible alarm. The loudspeaker 1202 of thesensor 550 may be used for the audible alarm or an additional speakermay be included loudspeaker and used for the audible alarm. The devicevibrating mechanism 3210 can also be used as an alarm. If a systemfailure is detected that requires immediate attention, both alarms canbe activated. Additionally, a secondary battery or supercapacitor may beemployed as a backup to the primary battery. If either battery fails,the controller can activate one or more alarms so that at least oneannouncement of battery failure occurs.

The alarms can also be used to indicate to a user that the device isworking properly. For example, a user might program the device for abolus delivery over a certain period of time. The user may desire toknow that the programmed delivery is occurring properly. The processorcan use the vibrating motor or an audio sound to indicate successfulprogrammed delivery. Thus, some mechanisms can be employed in someembodiments of the device to provide feedback, whether positive ornegative, to the patient or user.

A microphone may also be used to detect any abnormal vibration or lackof normal vibrations and trigger an alarm condition. In variousembodiments, a microphone of the acoustic volume sensing system may beused to perform such monitoring, or a separate microphone may beincluded for such monitoring. Periodic checks can also be performed todetermine that the device is operating by checking for expected pumpvibrations with the microphone. If improper vibrations are detected, orif proper vibrations are not detected by the microphone, an alarm can beactivated.

Referring now to FIG. 71, various components of a device 10 are shownschematically. In one embodiment of the device 10, a top X portion mateswith a base portion Y and a reservoir 20 is sandwiched between the top Xand base Y. The force of the sandwiching allows the reservoir septum6272 to mate with the base portion Y. In some embodiments, both aninfusion device 5010 and an analyte sensor 5020 are inserted through thebase Y and into a patient (not shown).

In many embodiments, the base Y and the reservoir 20 are disposableportions and the top X is a non-disposable portion. Both the infusiondevice 5010 and the analyte sensor are also disposable.

As previously discussed, the patch pump device may be entirely orpartially disposable. FIG. 72 shows an embodiment of a fluid deliverydevice 10 having disposable and non-disposable portions. In thisembodiment, the disposable portion Y contains components that come intodirect contact with the fluid, including the collapsible reservoir 20,pumping assembly (not shown), the variable volume dispensing chamber 122(part of the dispensing assembly 120, located on the top X) and the flowrestrictor (not shown), as well as one way valves (not shown) and afluid path (not shown) connecting the reservoir to the pumping mechanismto the variable volume dispensing chamber 122. Additionally, thedisposable portion Y includes a reservoir cavity 2645

The reusable portion X includes elements of the dispensing assembly 120except the variable volume dispensing chamber 122, which is located onthe disposable portion Y. In some embodiments, the dispensing assembly120 is an AVS assembly. The AVS assembly is described in detail above.Referring now to FIG. 73, an integrated acoustic volume measurementsensor is shown on a PCB.

Referring now to FIG. 74, the device 10 shown in FIG. 49 is shown. Thebase disposable portion Y includes a reservoir cavity 2645. The topnon-disposable portion X includes battery 15 and a dispensing assembly120. A microphone 133 is shown as well as a diaphragm spring 130. Insome embodiments, the dispensing assembly 120 includes more than onemicrophone. Although throughout this description, each microphone isreferred to as 133, this does not infer that the microphones are alwaysidentical. In some embodiments, the microphones are the same, in otherembodiments, the microphones are different.

In the FIG. 74, the top non-disposable portion X also includes main PCB13, a vibration motor 3210 and a pumping actuation member 54. The top,non-disposable portion X includes the AVS assembly or dispensingassembly 120. In FIG. 74, a microphone 133 is shown. The top,non-disposable portion X also includes a battery 15, which may be usedto provide electrical power to electronics on the non-disposable portionand/or the disposable portion. In some embodiments, this battery 15 isrechargeable. Recharging can be done by methods described below. Thedisposable portion Y includes the wetted components including a fluidline (not shown) and the pumping assembly. In FIG. 74, only the pumpingplunger 54 can be seen. This embodiment of the device 10 can alsoinclude many of the elements described above, including, but not limitedto, a fluid impedance, a flexible membrane, a cannula housing and asensor housing. Any pumping mechanism can be used.

Referring now to FIG. 75, the device 10 is shown in another view wheremore elements are visible. In FIG. 75, the device 10 is shown with basedisposable portion Y including a coiled microtubing flow restrictor 340and a fluid line 310 connecting the inlet 21 and outlet 22 valves. Thepumping actuation member 54 is also shown. The top X includes a main PCB13, a vibration motor 3210, two microphones 133, a speaker 134, areference chamber 127 and a fixed volume chamber 129. A battery 15 isalso shown. Since choosing a very small diameter for the flow restrictor340, may cause occlusion of the line 310 (for example, due to proteinaggregates in a therapeutic fluid), it may be desirable to use a longerlength of tubing with a larger diameter. However, in order to pack alonger length of tubing within a patch-sized housing, it may benecessary to bend the tubing in to form a tortuous path, e.g., a coiledor serpentine shape.

Referring now to FIG. 76, an exploded view of the device 10 shown inFIGS. 72, 74 and 75 is shown. The top, non-disposable portion X is shownseparated from the base disposable portion Y. In practice, a reservoir(not shown) would be placed in between the top X and base Y portions.Once the top X and base Y are assembled to form a device 10, thereservoir will become connected to the fluid line 310.

Referring now to FIG. 77, an exploded view of another embodiment of adevice 10 including a disposable base Y and non-disposable top X part isshown. Also included is a reservoir 20, an adhesive 3100 and a bridge5040 apparatus holding an infusion device 5010 and a sensor 5020. Thisdevice 10 includes a more rounded footprint and a dome shape. A battery15 and a main PCB 13 are shown located on the top X. The base Y includesa reservoir cavity 2645. An adhesive 3100 is shown in a two pieceembodiment. The bridge 5040 is used to insert the infusion device 5010and sensor 5020 through the base Y. The reservoir 20 is shown as havingan irregular shape, however, in other embodiments, the reservoir 20 canhave any shape and can vary in size according to the fluid capacitydesired. In this embodiment of the device 10, the non wetted componentsare in the top non-disposable X and the wetted components are in thebase disposable Y.

When assembled, the device 10 may be adhered together using a centerregion of the adhesive (not shown). Alternately, the device 10 may belocked together mechanically using any of many embodiments describedherein for latching. Although some embodiments are described belowherein, many others will be apparent and as the shape of the devicevaries, in many cases, the latch will also.

Referring now to FIG. 78, an exploded view of another embodiment of thedevice 10 is shown. The top non-disposable portion X is mostly domeshaped, however, a protrusion X1 is shown to accommodate the mechanismsinside the top X. Thus, the shape of the device can vary and can includepolyps and protrusions, dimples and other texture-like features toaccommodate various designs of the device.

The reservoir 20, infusion device 5010 and sensor 5020 are shown. Theinfusion device 5010 and sensor 5020 can be inserted through the base Yand into a patient (not shown). The base Y is shown with an adhesive3100 or pad 3220 underneath. In practice, the adhesive 3100 or pad 3220can be first adhered to the skin and base Y. Next, the infusion device5010 and sensor 5020 are inserted through the base Y into a patient (notshown, shown in FIG. 79 as 5020 and 5010). The reservoir 20 is thenplaced into the reservoir cavity 2645 either by first placing thereservoir 20 into the top X then sandwiching the top X and the base Y,or, placing the reservoir 20 into the reservoir cavity 2645 and thensandwiching the top X and the base Y. Either way can be used. The finalresult is the reservoir 20 becomes connected to the fluid line (notshown) located in the base Y through a septum (shown upside down) on thereservoir 20 and a septum needle (not shown, see 6272). The top X isthen fastened to the base X either through use of an adhesive, or inthis embodiment, mechanically using a latch 654 to clamp the top X andbase Y together.

The base Y includes those components that are wetted. The base Y isdisposable. The top X includes non wetted components. The top X isnon-disposable. Referring now to FIG. 79, the base Y includes a variablevolume dispensing chamber 122, an inlet valve 21, and exit valve 22 anda pumping chamber 2350. As shown in this figure, those elements areshown as the membrane covering the area that acts as either the chambersor the valves. Thus, the base Y includes the membrane that securelymaintains the wetted areas, thus, maintaining the non wetted areas assuch in the top (not shown). As shown in FIG. 79, the sensor 5020 andthe infusion device 5010 have been inserted into their respectivehousings and through the base Y to the patient (not shown). The base Yis shown with the reservoir cavity 2645, but the reservoir (not shown)need to be connected so that the fluid lines from the reservoir to thechamber and to the infusion device are connected.

Referring now to FIG. 80, the top X of the device is shown. The top Xincludes those non wetted components including, as shown, a temperaturesensor 3216, a diaphragm spring 130, an inlet valve poppet 21, and exitvalve poppet 22 and a pumping actuation member 54. The top Y alsoincludes a relief 2640 to accommodate the reservoir (not shown).

Referring now to FIGS. 81A-81C, a sequence is shown to illustrate theprocess of sandwiching the reservoir 20 between the top X and base Y. Asseen in FIG. 81A, the top X as well as the reservoir 20 outside of thetop X are shown. The reservoir includes a septum 6270. The top Xincludes a reservoir relief 2640. Next, as shown in FIG. 81B, the top isprepared to sandwich with the base Y. Referring now to FIG. 81C, thereservoir 20 is placed, septum side down, inside the base Y. The septumwill connect with a cannulated septum needle (not shown) inside the baseY and connect the reservoir to the fluid line (not shown). In alternateembodiments, the reservoir may include a cannulated needle rather than aseptum and the fluid path may include a reservoir interface with aseptum rather than a cannulated needle.

Referring next to FIG. 82, the top X is shown with one embodiment of thepumping mechanism 16 exploded. The pumping mechanism 16 fits into thepumping mechanism housing 18 in the top X. The base Y is also shown aswell as one part of the latch 654 that will clamp the top X and base Ytogether.

Referring now to FIG. 83, the base Y is shown with the fluid pathassembly 166 as the membrane 2356 exploded from the base Y. Thisillustrates that in some embodiments of the device, the fluid pathassembly 166 is a separate part that is inserted into the base Y andsandwiched with the membrane 2356. Also shown in this figure, theadhesive or pad 3100/3220 in some embodiments, includes apertures forthe infusion device and sensor (not shown). Referring now to FIG. 84, abottom view of the base Y is shown. The bottom of the fluid pathassembly 166.

Referring now to FIGS. 85A and 85B, another embodiment of the device isshown. In this embodiment, the top X, also non-disposable, includes abolus button 654. The reservoir 20 is shown in an exploded view,however, in one embodiment, the reservoir 20 is built into the base Y.In another embodiment, the reservoir 20 is removable and placed into thereservoir cavity 2645 using a process similar to that described abovewith respect to another embodiment of the device.

The base Y is disposable and includes the wetted parts of the device 10.The sensor 5020, the cannula 5010, the variable volume dispensingchamber 122, the inlet valve area 21, the exit valve area 22 and thepumping chamber 2350. The volume dispensing chamber, the inlet valvearea 21, the exit valve area 22 and the pumping chamber 2354 are allcovered by membrane material, which may be in the form of a singlemembrane or distinct membranes.

The device 10 is clamped together by a latch mechanism 654 on the top Xand the base Y. Referring now to FIGS. 85C-85D, the device 10 is thelatching mechanism 654 is shown in an open position (FIG. 85C) and aclamped or closed position (FIG. 85D). The bolus button 3213, asdescribed in further detail above, can also be seen.

A cover (not shown) may be provided for use in any of the embodiments ofthe device, to replace the reservoir and top portion when the reservoiris removed while the base is connected to the patient. The cover wouldnot contain electrical components, thus, could be used in wetconditions. However, in some instances, the reservoir can be removedwithout the use of any cover.

Cannula and Inserter

FIG. 86A schematically shows a representative embodiment of the infusionand sensor assembly 5040 including both an infusion device, which can bea cannula or a needle 5010 and an analyte sensor, which includes asensor probe 5025 and a sensor base 5023. A bridge 5070 rigidly joins aninfusion cannula 5010 and the analyte sensor base 5023. The infusiondevice 5010 is bounded on an upper side by a septum 5060 which allowsfor fluid to flow from a source and be administered through an infusiondevice 5010 to a patient. The sensor base 5023 is the section of theanalyte sensor that is not inserted into the patient. In one embodiment,the base 5023 contains electronic contacts for the electrochemicalanalysis of blood glucose. A probe 5025 protrudes from the base 5023 ofthe analyte sensor 5020.

Referring now to FIG. 86B, in this embodiment, the infusion device 5010is a cannula that is introduced into the patient using an introducingneedle 5240. The introduction needle 5240 is inside the cannula 5010when being inserted into a patient. After insertion of the cannula 5010into the patient, the introduction needle 5240 is removed and the septum5060 is sealed to a fluid source, which, in some embodiments of thedevice described herein, is the fluid line. In some embodiments, thesensor probe 5025 is associated with an introduction needle 5072 whichaids in skin puncture for insertion of the sensor probe 5025. The sensorintroduction needle 5072, in some embodiments, at least partiallysurrounds the sensor probe 5025 while the sensor probe 5025 is beinginserted into a patient.

In other embodiments, the infusion device 5010 is a needle and does notrequire an introduction needle 5240. In these embodiments, the infusiondevice 5010 is inserted into the patient and the septum 5060 seals witha fluid source.

In both FIGS. 86A and 86B, upon both the infusion device 5010 and sensorprobe 5025 being lined up appropriately, force is applied to the bridge5070. This forces both the infusion device 5010 and sensor probe 5025into the patient. Once in the patient, releases 5052 are actuatedthrough holes, separating the infusion device 5010 and septum 5060, aswell as the sensor base 5023, from the bridge 5070. Referring to FIG.86B, where introduction needles 5240 and 5072 are used, they willtypically remain attached to the bridge 5070 following insertion.

The bridge can be made from any material desired, including plastic. Thecannula can be any cannula in the art. The septum 5060 can be made fromrubber or plastic and have any design capable of imparting the functionsdesired. In the embodiments where the infusion device is a needle, anyneedle may be used. In embodiments where introduction needles are used,any needle, needle device or introduction device can be used.

The infusion and sensor assembly requires force be applied in order tobe inserted into a patient. As well, the infusion and sensor assemblyrequires that the infusion device and sensor are released from theinfusion and sensor assembly. Thus, both the force and the release canbe actuated manually, i.e., a person performs these functions, or aninsertion device may be used to actuate the assembly properly. Referringnow to FIGS. 87A-87E, an example of an inserter 5011 that can bemanually operated is shown. The infusion device 5010 and sensor 5023 areheld by the bridge 5070. The inserter 5011 includes covers 5012 for boththe infusion device 5010 and the sensor 5023. As shown in FIGS. 87B-87E,using the inserter 5011, both the infusion device 5010 and the sensor5023 are inserted through a device 10. Although FIG. 87A shows thesharps exposed, in some embodiments, the covers 5012 completely encasethe sharps prior to the insertion process.

The inserter 5011 could be operated manually, but could also beincorporated into another inserter device such that a mechanicaladvantage can be applied. Referring now to FIGS. 88A-88B, one embodimentof an inserter device 5013 is used with an apparatus similar to theinserter 5012 shown in FIGS. 87A-87E. The mechanism of the inserterdevice 5013 is shown in FIGS. 88C-88D. An actuation lever 5014 eitherreleases a spring (as shown in FIGS. 88C-88D) or provides anothermechanical advantage that allows for the inserter 5012 to be insertedthrough a device (not shown). The inserter 5012 will thus release theinfusion device 5010 and sensor 5023 and then, the inserter 5012 caneither be removed from the inserter device 5013 and the inserter device5013 refilled, or, the inserter device 5013 and inserter 5012 can bediscarded.

Various insertion devices are described herein. However, in otherembodiments, different insertion devices are used or the infusion deviceand sensor are introduced manually.

Features may be included for securing the infusion and sensor assembly5040 to an automatic inserter. For example, the releases shown in FIGS.86A-86B as 5052 may receive pins of an automatic insertion device.Referring to both FIGS. 89A and 89B a representative embodiment of anautomatic inserter 5100 is shown. As shown in the front view of FIG.89A, the inserter 5100 includes pins 5130 which travel in pin slots 5140within an inserting cartridge recess 5120. In practice, the infusion andsensor assembly (not shown, shown in FIGS. 86A and 86B as 5040) ispressed into the cartridge recess 5120, causing pins 5130 to be insertedinto the holes in the infusion and sensor assembly (shown as 5052 inFIGS. 86A and 86B). As shown in the rear view of FIG. 89B, a cockinglever 5145 is used to ready the inserter 5100 for firing. The inserter5100 is then either held against the skin or aligned with a cannulahousing and sensor housing on a base (not shown) and fired by pressing atrigger 5110. Upon firing, the pins 5130 travel in their slots 5140,thereby forcing the infusion device and sensor (both not shown) into apatient. Inserter foot 5160 limits the downward travel of the infusionand sensor assembly. The inserter may also automatically withdraw theintroduction needles (not shown, see FIG. 86B) from the infusion andsensor assembly.

The infusion and sensor assembly may be preloaded in the inserter 5100prior to distribution to an end user. As shown in FIG. 90, in otherembodiments, a cartridge 5080 may be used to protect a user and toprotect the sharps held in the assembly shown as 5040 in FIGS. 56A and56B. Referring to both FIG. 90 and FIGS. 86A-86B and FIG. 89A, in thecartridge embodiment 5080, the infusion and sensor assembly 5040 isembedded in the cartridge 5080. The cartridge 5080 is mounted in thecartridge recess 5120. The pins 5130 may project through the holes 5052and into grooves 5090 in the cartridge 5080. Upon actuation of theinserter 5100, the pins travel within the grooves 5090 as the 5080travels toward the patient to insert the sharps. The cartridge 5080 maybe constructed of a rigid material.

Referring now to FIGS. 91A-91C, several views of an embodiment of aninserter mechanism for an inserter, such as the one shown in FIGS. 89Aand 89B as 5100, are shown. FIG. 91A shows a perspective view, FIG. 91Bshows a front view, and FIG. 91C shows a side view of one embodiment ofan inserter mechanism. The inserter 5100 has a cocking lever 5145, whichconnects via cocking linkages 5350 to a hammer cocking slide 5330, andis used to move the cocking slide 5330 to a charged position. A powerspring 5390 connects the hammer cocking slide 5330 to a trigger 5110and, when compressed, provides the downward force necessary forinsertion of an infusion device or an infusion and sensor assembly (notshown). A trigger hammer 5340 is disposed under the hammer cocking slide5330 and between a pair of cocking linkages 5350; the trigger hammer5340 transmits the kinetic energy that is released from the power spring5390 upon pressing the trigger 5110. The energized trigger hammer 5340impacts a cartridge bolt 5380, positioned below. The cartridge bolt 5380is linked to a cartridge housing 5370, which holds the cartridge, forexample, the one shown in FIG. 90. The cartridge bolt 5380 is alsodisposed atop a return spring 5360 for returning the cartridge housing5350 to a retracted position.

FIGS. 92A-92F schematically show a time sequence for the cocking andfiring of an inserter 5100 of the type described with reference to FIGS.91A-91C. FIG. 92A shows the inserter 5100 in a resting position.Lowering the cocking lever (not shown, see FIG. 91A 5145) causes thehammer cocking slide 5330 to lower and engage the trigger hammer 5340.FIG. 92B shows the hammer cocking slide 5330 in a lowered position inwhich it is engaged with the trigger hammer 5340. Raising the cockinglever causes the hammer cocking slide 5330 and hammer 5340 to be raised,thus compressing the power spring 5390; the resulting position is shownin FIG. 92C. After ensuring the proper positioning of the inserter 5100with respect to a base (not shown) and/or the skin of a patient, thetrigger is pressed, thereby sending the trigger hammer 5340 downward;FIG. 92D shows the trigger hammer 5340 in transit. As shown in FIG. 92E,the trigger hammer 5340 impacts the cartridge bolt 5380, causing it totravel downward, insert the needle or needles held in the cartridgehousing (not shown) and compress the return spring 5360. FIG. 92F showsthe return spring 5360 in the process of forcing the cartridge bolt 5380upward; this causes retraction of the cartridge housing and thecartridge contained therein (not shown) and any associated introductionneedles used.

Referring now to FIGS. 93A-93C, one embodiment of a temporal sequencefor inserting and securing an infusion device (i.e., cannula or needle5010) into a base Y is shown. FIG. 93A shows a base Y with a lockingfeature 5210 positioned above a cannula housing 5030. The base Y istypically positioned against the skin of a patient 5220 when insertingan infusion device or cannula 5010. FIG. 93B shows a cannula 5010 beingforced through the cannula housing 5030 in the base Y. In this figure,an introduction needle 5240 is used that traverses a septum (not shown)and is positioned coaxially in the cannula 5010; a sharp point of theintroduction needle 5240 emerges from the tip (not shown) of the cannula5010 to help puncture a patient 5220. The resilient locking feature 5210is pushed aside during insertion of the cannula 5010. FIG. 93C shows thecannula 5010 fully inserted through the cannula housing 5030 of the baseY, with the tip of the cannula fully inserted into the patient 5220. Theintroduction needle 5240 has been removed and the septum 5060 hasself-sealed to a fluid source or fluid line (not shown). The resilientlocking feature 5210 is engaged with the cannula 5010, therebypreventing the cannula 5010 from moving in relation to the base Y.Although FIGS. 93A-93C show a cannula 5010, the infusion and sensorassembly shown in FIG. 86B can be inserted using the locking feature5210 and method shown and described in FIGS. 93A-93C.

Referring now to FIGS. 92G-92H, an inserting cartridge bolt lockingmechanism for use with an inserter, such as the one shown in FIGS.91A-92F, as 5100 is shown. The cartridge bolt locking mechanism canfunction as an interlock to prevent accidental firing while themechanism is being cocked. The locking mechanism includes a catch 5420,which when engaged in a catch recess 5410, prevents downward movement ofthe cartridge bolt 5380. As shown in FIG. 92G, when the cocking lever5145 is in a closed position, the cocking lever 5145 contacts a catchlever 5440, which rotates the catch 5420 and prevents the catch 5420from inserting into the catch recess 5410. A catch spring 5430, disposedbetween the catch 5420 and a catch spring support 5450, is in acompressed positioned. The cartridge bolt 5380 and trigger hammer 5340are free to move. As shown in FIG. 92H, when the cocking lever 5145 isrotated into a downward position, the catch lever 5440 is released,thereby allowing the catch spring 5430 to force the catch 5420 to insertinto the recess (here the catch 5420 is shown inside the recess, but therecess is shown in FIG. 92G as 5410); downward movement of the cartridgebolt 5380 is thereby prevented. Return of the cocking lever 5145 thenreturns the catch 5420 to an unlocked position. The cartridge bolt 5380is then free for downward movement in the triggering process.

Referring now to FIGS. 94A-94C, one embodiment of the process of matinga cannula 5010, where the cannula is a traditional cannula requiring anintroduction needle (as shown in FIG. 86B) to the base Y and establishesfluid communication with a fluid line 310 is shown. FIG. 94A shows asectional view of a cannula 5010 with two septa: an introduction needleseptum 5062 and a fluid line septum 5270. The introduction needle septum5062 seals a passageway 5280 leading to the hollow needle (not shown,shown in FIG. 94B as 5290) of the cannula 5010. A cannula introductionneedle 5240 is shown positioned above the introduction needle septum5062 and just prior to insertion of the introduction needle 5240.

Referring now to FIG. 94B, the introduction needle 5240 is showninserted through the introduction needle septum 5062. A user mates thecannula 5010 into the base Y, which has an upwardly-pointing rigid,hollow needle 5290. During insertion of the cannula 5010 into the baseY, the introduction needle 5240 punctures the fluid line septum 5270 toestablish fluid communication between the fluid line 310 and thepassageway 5280. If the base Y is held against a patient (not shown)during insertion of the cannula 5010 into the base Y, fluidcommunication between the fluid line 310 and the passageway 5280 will beestablished at about the same time that the patient's skin is pierced.Referring now to FIG. 94C, the cannula 5010 is shown, fully insertedinto the base Y, with the introduction needle removed and fluidcommunication established with the fluid line 310.

In an alternate embodiment, insertion of an infusion device and/orsensor is assisted by a vibration motor coordinated with a fluiddelivery device. Simultaneously with the insertion of the infusiondevice and/or sensor, a vibration motor may be activated.

Adhesion

Referring now to FIG. 95 a top perspective view of one embodiment of anadhesive patch 3100 for securing an object, such as a fluid deliverydevice 10, to the skin of a patient (not shown) is shown. Although theadhesive patch 3100 is shown in the present shape, other shapes can beused. Any adhesive patch 3100 that can securely hold a fluid deliverydevice can be used.

Fluid delivery device 10 is securely held under a central region 3130 ofthe adhesive patch 3100, which is attached to the skin of a patient byadhesive members 3111. These adhesive members 3111 emanate from acentral region 3130 in a radial pattern and are spaced apart from eachother by intervening regions 3121. The radial arrangement of theadhesive members 3111 allows for attachment of the device 10 to thepatient in secure manner. In some embodiments, the central region 3130covers the entire device 10, however, in other embodiments, the centralregion 3130 covers a portion of the device 10. The central region 3130may also include interlocking attachment features (not shown) that maybe held by complementary interlocking features (not shown) of the device10. In an alternate embodiment, the device 10 is securely attached atopthe central region 3130 (for example, by an adhesive or interlockingfeature).

The adhesive patch 3100 is typically flat and composed of a polymericsheet or fabric. The adhesive patch 3100 may be supplied with adhesiveaffixed on one side and protected by a peelable backing such as apeelable sheet of plastic to which the adhesive will adhere more looselythat to the patch 3100. The backing may be a single continuous piece, ormay be divided into regions that may be removed separately.

In a illustrative embodiment, the backing for the central region 3130may be removable without removing the backing to the adhesive members3111. To use the adhesive patch 3100, a user removes the backing of thecentral region 3130 and presses the device 10 against the newly exposedadhesive of the central region to attach the device 10 to the centralregion 3130. The user then places the device against the skin, removesthe backing from an adhesive member 3111, affixes the adhesive member tothe skin, and repeats the affixation process with additional members. Auser may affix all of the adhesive members 3111 or only some of themembers, and save additional adhesive members 3111 for application onanother day. Since adhesives typically used for attachment to skin onlyremain securely attached for several days, application of sets ofadhesive members 3111 on different days (for example, staggered by 3 to5 days) should extend the amount of time that the device 10 remainssecurely attached to the skin and reduce the of time, expense anddiscomfort that is often involved in reapplication of the device. Thevarying tabs may have indicia such as different colors or numbers toindicate to the appropriate time to affix the various adhesive members3111. The adhesive members 3111 may include perforations to render themfrangible with respect to the central region 3130 so that used adhesivemembers may be removed after use. Additional embodiments for extendingthe duration during which device 10 remains affixed are discussed abovewith reference to FIGS. 79-83.

FIG. 96 schematically shows a sectional view of a fluid delivery device10, with an inserted cannula 5010, held securely under an adhesive patch3100. A pad 3220 may be included between the device 10 and a patient'sskin 3250 and allow air to flow to the skin. Air flow to skin may beincreased by the inclusion of passageways 3230 in the pad 3220.Passageways 3230 may also be formed by using multiple pads that arespaced apart or by constructing pad 3220 from a highly porous material.Thus, the pad 3220 can be any shape and size and in some embodiments,the pad 3220 is made up of a number of separate pieces. Pads 3220 may beeither adhered to the underside of the device 10 during manufacture ormay be adhered to the device 10 by a user. Alternately, the pad 3220 maybe loosely placed onto the skin by a user prior to application of theadhesive patch 3100. The pad 3220 may include a compliant material, suchas porous polymeric foam.

FIG. 97 shows an embodiment of the invention that uses a first adhesivepatch 3100 and an additional adhesive patch 3300 to secure a device (notshown) to a patient. First, a device (not shown) is positioned for useand secured to the skin (not shown) of a patient with an adhesive patch3100 using tab-like adhesive members 3111. The central region 3130 maybe positioned atop (as shown), or secured below, the device. After aperiod of time, either prolonged or short, a second adhesive patch 3300is positioned so that its central region sits atop the first adhesivepatch 3100 and the second adhesive patch's adhesive members 3320 aresecured to the skin of the patient in the intervening regions betweenthe first adhesive patch's adhesive members 3111. Frangible regions maybe provided to aid in the removal of loose or unwanted adhesive members3111 associated with the earlier placed patch 3100.

Referring now to both FIGS. 98 and 99, embodiments in which an adhesivepatch 3100 has been divided into at least two smaller adhesive patchesare shown. In these embodiments, the adhesive patch 3100 is divided intotwo adhesive patches, 3410 and 3420, each having adhesive members 3111radially arranged around a central void 3430. The two adhesive patches,3410 and 3420, each span a semi-circle of about 180°, but otherconfigurations could be used such as: three patches, each spanning 120,°or four patches each spanning 90°. In some embodiments, the adhesive caninclude greater than four patches. The configurations described withrespect to these embodiments follow the formula 360°/n where n is thenumber of patches. But, in other embodiments, depending on the shape ofthe device, the formula shown and described here does not apply. Instill other embodiments, the patches may also cover more than 360°, andthus overlap.

As shown in the perspective view of FIG. 99, due to the presence of acentral void (not shown, shown in FIG. 98), the central region 3130 isin the form of a thin strip for adherently positioning along theperimeter of the device 10. The two patches, 3410 and 3420, togethersecurely attach the device 10 to the skin (not shown). As in theembodiment described with reference to FIG. 95, air may flow between theadhesive members 3111 and under the device 10, especially if passageways3230 are provided.

FIG. 100 shows a perspective view of an embodiment that includes usingthe multiple adhesive patches to extend the time during which a device10 remains adhered to a patient (not shown) before removal. One of themultiple partial adhesive pads 3420 is removed while the device 10 isheld in place (either by a remaining adhesive patch 3410 and/or by auser). The removed adhesive patch 3420 is then replaced with a freshreplacement adhesive patch (not shown). The replacement adhesive patchmay be identical to the removed pad 3420 or may have adhesive members3111 that are positioned in an alternate configuration to allow adhesionto the fresh skin between the areas previously covered by adhesive patch3420. The remaining adhesive patch 3410 may then be replaced in asimilar manner. Indicia such as color coding may be used to indicate theage of the adhesive patches. The patches may also have a color changemechanism to indicate that their useful life has expired. Decorativepatterns, such as images and designs, may be included on the patches.

FIG. 101 schematically shows an embodiment in which multiple adhesivemembers 3111 are affixed to a patient 12 and also connected to a ringlike central region 3130 via tethers 3730. The tethers 3730 may befibers or cords and may be resilient to decrease the movement of thedevice 10 in response to movement of the patient 12. The use of tethers3730 also increases options available for skin positions of the adhesivemembers 3111.

The adhesive used in the embodiments described in FIGS. 95-101 can beany effective and safe adhesive available for use on a patient's skin.However, in one embodiments, the adhesive used is 3M product number9915, value spunlace medical non woven tape.

Clamping and Latching

FIGS. 102A-102C schematically show one mechanism for clamping orlatching together a top portion and a base portion of a fluid deliverydevice. Referring first to FIG. 102A, an elevation view of a clamp 6410is shown. FIG. 102B shows a base portion Y with keyholes 6440 for twoclamps; corresponding keyholes may also be included in the top portion(not shown). Referring now to FIG. 102C, the top X and the base Y may bealigned and a clamp 6410 may be inserted through the keyholes (notshown, shown in FIG. 102B as 6440). Rotating the clamp 6410 by 90°causes a stud bar 6430 to move into a locking position. Depressing a camlever 6400 engages a cam 6415, that is hingedly connected to a clamp pin6420, to push against the top X. As a result, the top X and the base Yare held with a clamping force between the cam 6415 and the stud bar6430. Raising the cam lever 6400 releases the clamping force and theclamp 6410 may be rotated by 90° and withdrawn to allow disassembly ofthe top X and base Y. In some embodiments, the lever may act as aprotective cover for the top X.

An alternate embodiment for clamping together the portions of a deviceis shown in FIGS. 103A-103D. FIG. 103A shows a perspective view and FIG.103B shows a top view of a cam guide 6500. The cam guide 6500 has akeyhole 6440 and sloped surfaces 6510. FIG. 103C shows a cam follower6520 having a central pin 6540 with a head 6560 attached at a first endand a bar 6550 attached to an opposite end. As shown in the sectionalview of FIG. 103D, the cam follower (not shown, shown in FIG. 103C) maybe inserted into keyholes (not shown, shown in FIG. 103C) in the top X,base Y, and cam guide 6500. Movement of a lever 6530 attached to thecentral pin 6540 causes rotation of the cam follower (not shown, shownin FIG. 103C), causing the bar 6550 to travel along the sloped surface(not shown, shown in FIG. 103C as 6510) and thereby transforming therotational force to a force which clamps the base Y and top X firmlybetween the cam follower head 6560 and the bar 6550.

Reservoir

Exemplary embodiments of collapsible reservoirs for holding fluids areshown in FIGS. 104-106C. The collapsible reservoir has at least onesection or wall that collapses as fluid is withdrawn, therebymaintaining ambient pressure in its interior. In most embodiments, asealable port (e.g., a septum) is included in the reservoir. The portallows the reservoir to be filled with fluid by a syringe and also, fora leak free connection to a fluid line. Alternately, an adaptor may beused to connect the reservoir with the fluid line. Alternately, as shownabove with reference to FIG. 71, a needle may be associated with thereservoir and a septum may be associated with the terminus of the fluidline. The reservoir may be constructed of a plastic material known to becompatible, even if for a very short duration, with the fluid containedin the reservoir. In some embodiments, the reservoir is entirelycollapsible, i.e., the reservoir does not include any rigid bodysurfaces.

Referring now to FIG. 104 a sectional view of a reservoir 20 is shown. Acavity 2645 for holding a volume of fluid is formed between a rigidreservoir body 6200 and a flexible reservoir membrane 6330. The flexiblemembrane 6330 is sealingly attached around the periphery of the cavity2645 to hold fluid within the cavity 2645. The flexible membrane 6330imparts collapsibility to the reservoir 20; it deforms inwardly as fluidis pumped from the cavity 2645.

A septum 6270 is seated in a neck 6240 extending from the body 6200. Theseptum 6270 serves as an interface between the cavity 2645 and a fluidline. In some devices, the fluid line terminates in a needle (notshown). In these embodiments, the needle may be inserted through theseptum 6270 to access a needle chamber 6280 portion of the cavity 2645.The septum 6270 location can be maintained by its location between a cap6250 and a ledge (not shown) formed at the junction of the inner wall6281 of the needle chamber 6280 and the cap bore 6282. The cap 6250 maybe held by a friction fit within the cap bore 6282. Upon insertion ofthe cap 6250, its position is limited by the wall 6261 of the cap bore6282. The portion of the cap 6250 closest to the septum 6270 may have acentral aperture to allow insertion of the needle through the cap 6250and into the septum 6270. Alternately, the cap 6250 may be punctured bythe needle.

FIG. 105 shows a perspective view of the inside of the collapsiblereservoir 20. A rim 6230 allows attachment of the flexible reservoirmembrane, which may be attached by welding, clamping, adhering, or othersuitable method to create a fluid tight seal. A guard structure 6290 maybe included to allow fluid to flow to or from the cavity 2645, butprevents a needle from entering the cavity, thereby preventing it frompossible puncture of the reservoir membrane.

FIGS. 106A-106C show an alternate embodiment of a reservoir in which acap 6250 sealingly attaches a septum 6270 to a wall 6320 of a reservoir.The wall 6320 could be constructed, for example, from a flexible sheetsuch as PVC, silicone, polyethylene or from an ACLAR film. In someembodiments, the wall 6320 may be constructed from a heat formablepolyethylene laminate formed with an ACLAR firm. The flexible sheet iscompatible with the fluid. The wall may be attached to a rigid housing,or part of a flexible plastic pouch, such as may be formed by foldingand welding the ends of a plastic sheet. FIG. 106A shows the cap 6250sealed to a wall 6320 via a circular fin 6350. The septum 6270 may beinserted into a turret 6340 that protrudes from the cap 6250. The turret6340 may be constructed from a material that is deformable at hightemperature, but rigid at room temperature, for example, low densitypolyethylene. Referring now to FIG. 106B, a hot press 6310, or anotherapparatus or process for melting, is used to melt or bend the turret6340 over the septum 6270. Referring now to FIG. 106C, the septum 6270is shown immobilized to the cap 6250.

Certain fluids are sensitive to storage conditions. For example, insulinmay be somewhat stable in the glass vials in which it is typicallyshipped, but may be unstable when left in prolonged contact with certainplastics. In some embodiments, the reservoir 20 is constructed of such aplastic. In this case, the reservoir 20 may be filled with fluid justprior to use so that the fluid and plastic are in contact for a shorterperiod time.

Reservoir Filling Station

Referring now to FIG. 107 a reservoir filling station 7000 for filling areservoir 20 with a fluid is shown. The fluid may be withdrawn from itsoriginal container with a syringe 7040 and introduced into the reservoir20 by using the fill station 7000. The fill station 7000 may include asubstantially rigid fill station base 7010 hinged to a substantiallyrigid fill station cover 7020 via a hinge 7030. Accordingly, the station7000 may be opened and closed to accept and hold the reservoir 20. Aneedle 7050 attached to the syringe 7040 may then be inserted through afilling aperture 7060 in the cover 7020, and through the reservoirseptum 6270. Since the fill station cover 7020 is rigid, it establishesa limit of travel upon the syringe 7040 and therefore controls the depthof needle 7050 penetration into the reservoir 20 to discourage punctureof the underside of the reservoir 20. A leg 7070 holds the station 7000in a tilted position when supported on a surface. Since the station 7000is tilted, as the fluid is injected from the syringe 7040 into thereservoir 20, air will tend to rise upwardly toward the septum 6270.After the syringe 7040 injects the desired amount of fluid into thereservoir 20, the syringe 7040 may be used to remove any remaining airin the reservoir 20. Since the fill station base 7010 and cover 7020 arerigid, the flexible reservoir 20 generally cannot be distended past afixed volume and overfilling of the reservoir 20 is discouraged. Thebase 7010 and cover 7020 may be locked together with a clasp, or a heavycover may be used to further discourage overexpansion and overfilling ofthe reservoir.

Referring now to FIGS. 108A and 108B, an alternate embodiment of thereservoir filling station 7000 is shown. In this embodiment, thereservoir (not shown) is placed in the space between the cover 7020 andthe base 7010. A hinge 7030 attached the cover 7020 and the base 7010.As shown in FIG. 108B, the reservoir (not shown) is inside, and asyringe (not shown) needle (not shown) is inserted into the fillingaperture 7060. The filling aperture 7060 connects directly to thereservoir's septum (not shown). A viewing window 7021 indicates thefluid line in terms of the volume of fluid that has been injected intothe reservoir.

A fluid delivery system typically includes a fluid delivery device andan external user interface, although in some embodiments a complete orpartial internal user interface is included in the device. The devicecan be any device as described herein or a variation thereof.

FIG. 109A shows a flow diagram of a data acquisition and control schemefor an exemplary embodiment of a fluid delivery system. A patient orcaregiver utilizes an external user interface 14 which is typically abase station or hand held unit housed separately from the fluid deliverydevice 10. In some embodiments, the user interface 14 is integrated witha computer, cell phone, personal digital assistance, or other consumerdevice. The user interface assembly may be in continuous or intermittentdata communication with the fluid delivery device 10 via wireless radiofrequency transmission (for example, via LF, RF, or standard wirelessprotocols such as “Bluetooth”) but could also be connected via datacable, optical connection or other suitable data connection. Theexternal user interface 14 communicates with a processor 1504 to inputcontrol parameters such as body mass, fluid dose ranges or other dataand receives status and function updates such as the presence of anyerror conditions resulting from occluded flow, leaks, empty reservoir,poor battery condition, need for maintenance, passage of an expirationdate, total amount of fluid delivered or remaining or unauthorizeddisposable component. The interface 14 may transmit error signals to apatient's guardian or medical professional through a telephone, email,pager, instant messaging, or other suitable communication medium. Areservoir actuator assembly 1519 includes an actuator 1518 and areservoir 1520. The dispensing assembly 120 transmits data related toflow through the flow line to the processor 1504. The processor 1504uses the flow data to adjust the action of the actuator 1518 in order toincrease or decrease flow from the reservoir pump assembly 1519 toapproximate the desired dosage and timing. Optionally, a feedbackcontroller 1506 of the processor 1504 may receive data related to theoperation of the reservoir pump assembly 1519 for detection ofconditions such as open or short circuit faults, or actuatortemperature.

FIG. 109B shows an alternate embodiment of the flow diagram in FIG.102A. In this embodiment, the lack of dispensing assembly/sensor removesthe feedback based on volume of fluid.

Referring now to FIG. 110A, a flow chart of one embodiment of theoverall operation of a fluid delivery device within the fluid deliverysystem is shown. A user starts 2800 the system using a switch or from anexternal user interface (step 2800). The system initializes by loadingdefault values, running system tests (step 2810) and obtaining variableparameters such as desired basal and bolus doses. Variable parametersmay be selected by the user using the user interface, either using aninput device such as a touch screen on the user interface or by loadingsaved parameters from memory (step 2820). The actuator timing iscalculated based on the predicted or calibrated performance of the fluiddelivery device (step 2830). The dispensing assembly is initiated at thestart of the fluid delivery device activation (step 2840). Dispensingassembly data collection 2835 continues through actuation and delivery.During operation, the dispensing assembly provides data that allowsdetermination of the cumulative volume of fluid that has flowed throughthe dispensing chamber as well as the flow rate for one or more timeperiods. The fluid delivery device is activated to cause fluid to flowthrough the flow line into the dispensing chamber (step 2840). Drugflows from the dispensing chamber to the patient at a rate determined bythe impedance of the exit, and in some embodiments, the force exerted bya diaphragm spring, and the force exerted by the pumping assembly (step2860). The system will stop and the user will be notified if there is auser stop interrupt, a low flow condition, the reservoir is determinedto be empty based on predicted cumulative flow or detection by anadditional reservoir volume sensor, or any other alarm operation eitherpart of the system or user specified (step 2870). If there is no userstop signal, determination of an empty reservoir or another alarmindicator, then a check is made to determine if an adjustment to theactuator timing is needed due to a deviation between the actual anddesired flow rate or due to a change in desired flow rate by the user(step 2880). If no adjustment is needed, the process returns to step2840. If an adjustment is needed, the process instead returns to step2830. Referring now to FIG. 110B, a flow chart of another embodiment ofthe overall operation of a fluid delivery device within the fluiddelivery system is shown. In this embodiment, the decision to adjust theactuation timing is made based on a user inputted variation or onanother feedback. In this embodiment, a dispensing assembly with asensor for determining volume is not included; thus the adjustments aremade based on alternative feedback mechanisms.

Wireless Communication

Referring now to FIG. 111 a layout of an embodiment using coils forinductive charging and wireless communication in a fluid delivery systemis shown. As previously described, the user interface assembly 14 can beembodied as a hand held user interface assembly 14 that wirelesslycommunicates with the fluid delivery device 10. A secondary coil (i.e. asolenoid) 3560 may be employed in the fluid delivery device 10 as awireless transceiver antenna in conjunction with wireless controller3580. The secondary coil 3560 may also serve as a secondary transformerfor recharging the device battery 3150, at least partially, inconjunction with a battery recharging circuit 3540. In this embodiment,the user interface assembly 14 contains a primary coil 3490 forinductively coupling energy to a secondary coil 3560. When the userinterface assembly 14 is in close proximity to the fluid delivery device10, the primary coil 3490 energizes the secondary coil 3560. Theenergized secondary coil 3560 powers a battery recharging circuit 3540for recharging the battery 3150 in the fluid delivery device 10. In someembodiments, the primary coil 3490 also functions as an antenna totransmit and receive information from the fluid delivery device 10 inconjunction with a wireless controller 3470.

Referring now to FIG. 112, some embodiments include long range wirelesscommunication (e.g., 20-200 ft or more) hardware in the fluid deliverydevice 10. Thus, the fluid delivery device 10 could be monitored from adistance.

Still referring to FIG. 112, an intermediate transceiver 6600, typicallycarried by the patient, can provide the benefits of long rangecommunication without increasing the size, weight and power consumptionof the fluid delivery device 10. As shown in the data flow diagram ofFIG. 112, a wearable fluid delivery device 10 uses short range hardwareand associated software to transmit data to, or receive data from, theintermediate transceiver 6600. For example, the device 10 may beequipped to transmit data over distances of approximately 3-10 ft. Theintermediate transceiver 6600 may then receive this data and use longrange hardware and software to relay this data to a user interfaceassembly 14. The intermediate transceiver 6600 may also accept controlsignals from the user interface assembly 14 and relay these signals tothe device 10. Optionally, the user interface assembly 14 may also becapable of communicating directly with the fluid delivery device 10,when in range. This direct communication may be configured to occur onlywhen the intermediate transceiver 6600 is not detected, oralternatively, anytime the user interface assembly 14 and the fluiddelivery device are within range of each other.

Manytypes of data may be transmitted in this way, which include, but arenot limited to:

Data related to the timing of pump actuation and volume measurements andother data from the dispensing assembly may be transmitted to theintermediate transceiver 6600 and, in turn, to the user interfaceassembly 14;

Alarm signals may be transmitted to and from the fluid delivery device10;

Signals to confirm the receipt of data may be transmitted from the userinterface 14 to the intermediate transceiver 6600 and from theintermediate transceiver 6600 to the fluid delivery device 10;

Control signals to change the operating parameters of the device 10 maybe transmitted from the user interface assembly 14 to the fluid deliverydevice 10 using the intermediate transceiver 6600.

Referring now to FIG. 113, a plan diagram of a specific embodiment of anintermediate transceiver 6600 is shown. A short range transceiver 6610communicates with a nearby fluid delivery device. The short rangetransceivers of the device and the intermediate transceiver 6600 maycommunicate using one or more of many protocols and transmissionfrequencies known to be useful for short range communication, e.g. radiofrequency transmission. Data received by the intermediate transceiver6600 is conveyed to a microprocessor 6630, which may store the data inmemory 6620 (e.g., a flash memory chip), and retrieve the data asneeded. The microprocessor 6630 is also connected to a long rangetransceiver 6640, which is in data communication with the userinterface. For example, the intermediate transceiver 6600 and userinterface assembly may operate on the Bluetooth standard which is aspread-spectrum protocol that uses a radio frequency of about 2.45 MHzand may operate over a distance of up to about 30 feet. The Zigbeestandard is an alternative standard that operates in the ISM bandsaround 2.4 GHz, 915 MHz, and 868 MHz. However, any wirelesscommunication could be used.

Optionally, the microprocessor 6630 analyzes received data to detect thepresence of malfunctions or maintenance needs associated with thedevice. Some examples of fault conditions include, but are not limitedto:

a lack of received data for a time period that exceeds a set limit;

a lack of data receipt confirmation signal from the device or the userinterface assembly;

an overflow or near overflow condition of the appliance memory 6620;

low power;

overly high, low or improperly timed volume measurements received fromthe fluid delivery device 10.

Based on this fault analysis, the microprocessor 6630 may trigger analarm 6650 (e.g., a bell or buzzer). The microprocessor 6630 may alsocommunicate an alarm condition to a remote device. The remote device maybe, for example, the user interface assembly using the long rangetransceiver 6640, the fluid delivery device 10 using the short rangetransceiver, or both the user interface assembly and fluid deliverydevice. Upon receiving an alarm signal, the user interface assembly maythen relay the alarm signal over longer distances to a medicalprofessional or patient guardian (e.g., by pager or telephone call orother methods of communication).

The power supply 6670 may be rechargeable, and may store sufficientenergy to operate continuously for a period of time, for example, atleast 10 hours. However, the operation time will vary based on use anddevice. The size of the fluid delivery device may be reduced so that itmay easily be carried in a pocket, purse, briefcase, backpack or thelike. One embodiment of the device includes a means to withstand routineshocks or spills. Additional features may be included in someembodiments, including, but not limited to, decorative features, or anyof a wide range of consumer electronics capabilities such as the abilityto play video games, send and receive instant messages, watch digitalvideo, play music, etc. Third party controls may be included to removeor limit the use of such functions during some or all hours of the day.Alternately, the device may be as small and simple as possible, and onlyserve to repeat short range signals over a longer range. For example,the memory and analysis capability may be omitted.

Referring now to FIG. 114, a data flow diagram for an embodiment of thesystem is shown. An intermediate transceiver 6600 is shown operating asa universal patient interface that engages in short range communicationwith multiple devices and relays information from those devices over along range to one or more user interfaces associated with those devices.Examples of devices include wearable, implantable or internal medicaldevices including a fluid delivery system, a glucose sensor, a kneejoint with an integrated strain sensor, an instrumented enteric probe inpill form, a defibrillator, a pacemaker, and other wearable therapeuticdelivery devices. Since different types of devices and devices fromdifferent manufacturers may utilize differing short range communicationstandards and frequencies, the intermediate transceiver 6600 may includehardware (e.g., multiple antennas and circuitry), and software tosupport multiple protocols.

Battery Recharger

Referring now to FIGS. 115 and 116. One embodiment of an apparatus isshown for recharging the battery 7100. In FIG. 15, the top,non-disposable portion of a fluid delivery device 2620 is showndisconnected from the base, disposable portion of a fluid deliverydevice. The battery recharger 7100 is used to recharge the battery (notshown) in the top 2620. In FIG. 116, the top 2620 is shown on thebattery recharger 7100. The latches 6530 are shown closed, connectingthe top 2620 to the battery recharger 7100. Thus, the latch 6530 used toconnect a top portion 2620 to a base portion (not shown) is also used toconnect the top 2620 to the battery recharger 7100. Docking mayestablish a direct power connection, or power may be transferred by wayof inductive coupling. Also, in some embodiments of the system, thepatient employs multiple non-disposable portions 2620 in rotation; i.e.,recharging one non-disposable portion 2620, while using a secondnon-disposable portion (not shown).

The various embodiments described herein include different types andconfigurations of elements such as, for example, pump architectures,pump actuators, volume sensors, flow restrictors, reservoirs (andreservoir interfaces), sharps inserters, housings, latching mechanisms,user interfaces, on-board peripherals (e.g., controllers, processors,power sources, network interfaces, sensors), and other peripherals(e.g., hand-held remote controller, base station, repeater, fillingstation). It should be noted that alternative embodiments mayincorporate various combinations of such elements. Thus, for example, apump architecture described with reference to one embodiment (e.g., thepump shown and described with reference to FIGS. 15A-15D) may be usedwith any of the various configurations of pump actuators (e.g., singleshape-memory actuator with single mode of operation, single shape-memoryactuator with multiple modes of operation, multiple shape-memoryactuators of the same size or different sizes), and may be used indevices with various combinations of other elements (or absence of otherelements) and/or any of the various flow restrictors.

Furthermore, while various embodiments are described herein withreference to a non-pressurized reservoir, it should be noted that apressurized reservoir may be used in certain embodiments or undercertain conditions (e.g., during priming and/or air purging). Amongother things, a pressurized reservoir might facilitate filling of thepump chamber, for example, following retraction of the pump actuationmember 54 shown and described with reference to FIGS. 15A-15D.

Additionally, while various embodiments are described herein withreference to a pump motor disposed in a reusable portion of a housing,it should be noted that a pump and/or a pump motor may alternatively besituated in the disposable portion, for example, along with variouscomponents that come into contact with the fluid. As with some of theother motors described herein, a motor disposed in the disposableportion may include one or more shape-memory actuators.

It should be noted that section headings are included for convenienceand are not intended to limit the scope of the invention.

In various embodiments, the herein disclosed methods including those forcontrolling and measuring flow of a fluid and for establishingcommunication amongst linked components may be implemented as a computerprogram product for use with a suitable controller or other computersystem (referred to generally herein as a “computer system”). Suchimplementations may include a series of computer instructions fixedeither on a tangible medium, such as a computer readable medium (e.g., adiskette, CD-ROM, ROM, EPROM, EEPROM, or fixed disk) or transmittable toa computer system, via a modem or other interface device, such as acommunications adapter connected to a network over a medium. The mediummay be either a tangible medium (e.g., optical or analog communicationslines) or a medium implemented with wireless techniques (e.g.,microwave, infrared or other transmission techniques). The series ofcomputer instructions may embody desired functionalities previouslydescribed herein with respect to the system. Those skilled in the artshould appreciate that such computer instructions can be written in anumber of programming languages for use with many computer architecturesor operating systems.

Furthermore, such instructions may be stored in any memory device, suchas semiconductor, magnetic, optical or other memory devices, and may betransmitted using any communications technology, such as optical,infrared, acoustic, radio, microwave, or other transmissiontechnologies. It is expected that such a computer program product may bedistributed as a removable medium with accompanying printed orelectronic documentation (e.g., shrink wrapped software), preloaded witha computer system (e.g., on system ROM, EPROM, EEPROM, or fixed disk),or distributed from a server or electronic bulletin board over thenetwork (e.g., the Internet or World Wide Web). Of course, someembodiments of the invention may be implemented as a combination of bothsoftware (e.g., a computer program product) and hardware. Still otherembodiments of the invention are implemented as entirely hardware, orsubstantially in software (e.g., a computer program product).

It should be noted that dimensions, sizes, and quantities listed hereinare exemplary, and the present invention is in no way limited thereto.In an exemplary embodiment of the invention, a patch-sized fluiddelivery device may be approximately 6.35 cm (˜2.5 in) in length,approximately 3.8 cm (˜1.5 in) in width, and approximately 1.9 cm (˜0.75in) in height, although, again, these dimensions are merely exemplary,and dimensions can vary widely for different embodiments.

While the principles of the invention have been described herein, it isto be understood by those skilled in the art that this description ismade only by way of example and not as a limitation as to the scope ofthe invention. Other embodiments are contemplated within the scope ofthe present invention in addition to the exemplary embodiments shown anddescribed herein. Modifications and substitutions by one of ordinaryskill in the art are considered to be within the scope of the presentinvention.

What is claimed is:
 1. A delivery device for delivering an infusionmedium to a user, the device comprising: a disposable housing assemblyadapted to be secured to a user's skin; a reservoir having an interiorfor containing a fluidic medium, the reservoir having an outlet port andbeing operatively coupled to a pumping assembly to selectively drivefluid out the outlet port from the reservoir interior; a base portioncomprising the reservoir, the base portion having a reservoir cavity,and a fluid path, the reservoir cavity comprising the outlet port and aseptum, the fluid path comprising a fluid channel from the outlet portto a cannula port; at least one flexible membrane portion attached ontothe base portion and forming a top of the reservoir cavity and a top ofthe fluid channel; and a tubing connected to the base portion at thecannula port, the tubing in fluid communication with the reservoircavity; and a needle insertion device for inserting a cannula into theuser's skin, the needle insertion device comprising an introductionneedle for movement between a retracted position and an extendedposition; wherein the disposable housing assembly has a passage throughwhich the introduction needle extends, and wherein the cannula has acentral passage through which the introduction needle extends.
 2. Thedelivery device of claim 1, further comprising a reusable housingassembly adapted to be secured to the disposable housing assembly, thereusable housing assembly comprising a volume sensing device, whereinthe volume sensing device determines the volume of fluid delivered tothe user.
 3. The delivery device of claim 2, the reusable housingassembly further comprising a latching mechanism for permittingselective engagement and disengagement with the disposable housingassembly.
 4. The delivery device of claim 2, the reusable housingassembly further comprising a mechanism for attaching the housingstructure to the user.
 5. The delivery device of claim 1, wherein thetubing portion comprises a cannula port end and a cannula interface end,the cannula interface end configured to attach to a cannula.
 6. Thedelivery device of claim 1, wherein the fluid path further comprises aseries of regions exposed to the flexible membrane portion, at least oneof the regions being a valve region.
 7. The delivery device of claim 6,wherein the series of regions further comprises a pump chamber region.8. The delivery device of claim 1, wherein the base portion and theflexible membrane portion constitute a fluidic assembly, and wherein thedisposable housing assembly further comprises a disposable base intowhich the fluidic assembly fits.
 9. The delivery device of claim 8,further comprising a pad coupled to a bottom of the disposable base, thepad for attaching the disposable housing assembly to the user.
 10. Thedelivery device of claim 1, wherein the reservoir port in fluidcommunication with the reservoir cavity and the septum for penetrationby a needle so as to fill the reservoir cavity with therapeutic fluid.11. A delivery device for delivering an infusion medium to a user, thedevice comprising: a disposable housing assembly adapted to be securedto a user's skin comprising: a bottom adapted for attachment to the skinof the user; a fluidic path portion having a reservoir, a pumpingchamber and an outlet; at least one flexible membrane portion forming atleast one portion of the fluidic path portion and the reservoir; atubing attached to the outlet, the tubing adapted to connect to acannula, wherein the reservoir having an interior for containing afluidic medium, the reservoir having an outlet port and beingoperatively coupled to a pumping assembly to selectively drive fluid outthe outlet port from the reservoir interior; and a needle insertiondevice for inserting the cannula into the user's skin, the needleinsertion device comprising an introduction needle for movement betweena retracted position and an extended position, wherein the disposablehousing assembly has a passage through which the introduction needleextends, and wherein the cannula has a central passage through which theintroduction needle extends.
 12. The delivery device of claim 11,further comprising a reusable housing assembly adapted to be secured tothe disposable housing assembly, the reusable housing assemblycomprising a volume sensing device, wherein the volume sensing devicedetermines the volume of fluid delivered to the user.
 13. The deliverydevice of claim 11, wherein the reservoir further comprises a septum,whereby the septum for filling the reservoir with therapeutic fluid. 14.The delivery device of claim 11, wherein the tubing further comprises anoutlet end and a cannula interface end, the outlet end attached to theoutlet and the cannula interface end configured to attach to a cannula.15. A delivery device for delivering an infusion medium to a user, thedevice comprising: a disposable housing assembly adapted to be securedto a user's skin comprising: a reservoir having an interior forcontaining a fluidic medium, the reservoir having an outlet port andbeing operatively coupled to a pumping assembly to selectively drivefluid out the outlet port from the reservoir interior; a substratehaving flexible membrane material thereon, and incorporating therein thereservoir and a fluid channel, the reservoir having a septum, the fluidchannel being part of a fluid path in the disposable housing assemblyfrom the outlet port to a cannula port and comprising a series ofregions exposed to the flexible membrane material, at least one of theregions being a valve region; and a tubing portion connected to thecannula port of the disposable housing assembly; and a needle insertiondevice for inserting a cannula into the user's skin, the needleinsertion device comprising an introduction needle for movement betweena retracted position and an extended position; wherein the disposablehousing assembly has a passage through which the introduction needleextends, and wherein the cannula has a central passage through which theintroduction needle extends.
 16. The delivery device of claim 15,further comprising a reusable housing assembly adapted to be secured tothe disposable housing assembly, the reusable housing assemblycomprising a volume sensing device, wherein the volume sensing devicedetermines the volume of fluid delivered to the user.
 17. The disposableunit of claim 16, further comprising a latching mechanism for permittingselective engagement and disengagement of the reusable housing assemblywith the disposable assembly.
 18. The delivery device of claim 15,wherein the tubing portion comprises a cannula port end and a cannulainterface end, the cannula port end attached to the cannula port and thecannula interface end configured to attach to a cannula.
 19. Thedelivery device of claim 15, wherein the fluid path further comprises apump chamber region.
 20. The delivery device of claim 15, wherein thetubing adapted to connect to a cannula.
 21. The delivery device of claim15, wherein the substrate and the flexible membrane material constitutea fluidic assembly, and wherein the disposable housing assembly furthercomprising a disposable base into which the fluidic assembly fits. 22.The disposable unit of claim 21, further comprising a pad coupled to abottom of the disposable housing assembly for attaching the housingstructure to the user.